DOE Office of Scientific and Technical Information (OSTI.GOV)

Pokharel, S; Rana, S

Purpose: purpose of this study is to evaluate the effect of grid size in Eclipse AcurosXB dose calculation algorithm for SBRT lung. Methods: Five cases of SBRT lung previously treated have been chosen for present study. Four of the plans were 5 fields conventional IMRT and one was Rapid Arc plan. All five cases have been calculated with five grid sizes (1, 1.5, 2, 2.5 and 3mm) available for AXB algorithm with same plan normalization. Dosimetric indices relevant to SBRT along with MUs and time have been recorded for different grid sizes. The maximum difference was calculated as a percentagemore » of mean of all five values. All the plans were IMRT QAed with portal dosimetry. Results: The maximum difference of MUs was within 2%. The time increased was as high as 7 times from highest 3mm to lowest 1mm grid size. The largest difference of PTV minimum, maximum and mean dose were 7.7%, 1.5% and 1.6% respectively. The highest D2-Max difference was 6.1%. The highest difference in ipsilateral lung mean, V5Gy, V10Gy and V20Gy were 2.6%, 2.4%, 1.9% and 3.8% respectively. The maximum difference of heart, cord and esophagus dose were 6.5%, 7.8% and 4.02% respectively. The IMRT Gamma passing rate at 2%/2mm remains within 1.5% with at least 98% points passing with all grid sizes. Conclusion: This work indicates the lowest grid size of 1mm available in AXB is not necessarily required for accurate dose calculation. The IMRT passing rate was insignificant or not observed with the reduction of grid size less than 2mm. Although the maximum percentage difference of some of the dosimetric indices appear large, most of them are clinically insignificant in absolute dose values. So we conclude that 2mm grid size calculation is best compromise in light of dose calculation accuracy and time it takes to calculate dose.« less

Comparative analysis of radioecological monitoring dosimeters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sobolev, A.I.; Pol`skii, O.G.; Shanin, O.B.

1995-03-01

This paper describes comparative estimates of radiation doses measured by two types of thermoluminescence dosimeters and two types of background radiation radiometers. The dosimetry systems were tested by simultaneously recording background radiation and standard radiation sources at a radioactive waste storage facility. Statistical analysis of the measurement results is summarized. The maximum recorded exposure dose rate for the experiment was 19 microrads per hour. The DTK-2 dosimeter overestimated dose rates by 6 to 43% and the DTU-2 dosimeter underestimated dose rates by 7 to 21%. Both devices are recommended for radioecological monitoring in populated areas. 4 refs., 3 figs., 5more » tabs.« less

Flu Vaccine and People with Egg Allergies

MedlinePlus

... 12 through 2014–15 reported maximum amounts of ≤1 µg/0.5 mL dose for flu shots and 0.24 µg/0.2 mL dose ... reactions, including anaphylaxis. In a Vaccine Safety Datalink study, there were ... other vaccines, (rate of 1.35 per one million doses). Most of these ...

Results from the first five years of radiation exposure monitoring aboard the ISS

NASA Astrophysics Data System (ADS)

Golightly, M.; Semones, E.; Shelfer, T.; Johnson, S.; Zapp, N.; Weyland, M.

NASA uses a variety of radiation monitoring devices aboard the International Space Station as part of its space flight radiation health program. This operational monitoring system consists of passive dosimeters, internal and external charged particle telescopes, and a tissue equivalent proportional counter (TEPC). Sixteen passive dosimeters, each consisting of TLD-100, TLD-300, TLD-600, and TLD-700 chips in a small acrylic holder, are placed throughout the habitable volume of the ISS. The TEPC and internal charged particle telescopes are portable and can be relocated to multiple locations in the Lab Module or Service Module. The external charged particle telescopes are mounted to a fixed boom attached to the starboard truss. Passive dosimeters were used in eleven monitoring periods over the period 20 May 1999 to 04 May 2003. Over this period exposure rates from TLD-100 measurements ranged from 0.120-0.300 mGy/d. Exposure rates inside the habitable volume are non-uniform: exposures vary by a factor of ˜ 1.7 from minimum to maximum, with the greatest non-uniformity occurring in the Lab Module. Highest daily exposure rates are near the window in the Lab Module, inside the Joint Airlock, and the sleep stations inside the Service Module, while the lowest rates occur inside the polyethylene-lined Temporary Sleep Station in the Lab Module, adjacent to the port ``arm'' of Node 1, and the aft end of the Service Module. The minimum exposure rates as measured by the passive dosimeters occurred in the spring of 2002, very close to the solar F10.7 emission maximum (Feb 2002), and two years after the sunspot maximum (Apr 2000). Exposure rates have since gradually increased as the sun's activity transitions towards solar minimum conditions. Since 01 Jun 2002, dose rates measured by the IV-CPDS, estimated from the count rate in first detector of the telescope's stack, ranged from ˜ 0.170-0.390 mGy/d. The maximum measured dose rate occurred 28 Oct 2003 during the ``Halloween'' space weather event. Interestingly, the minimum dose rate occurred 31 Oct 2003, near the end of the same remarkable space weather event, when the Earth was experiencing a significant Forbush decrease. The average IV-CPDS-measured dose rate increased from 0.194 to 0.234 mGy/d since 01 Jun 2002--an increase of ˜ 21% and a further indication that the low-Earth radiation environment is transitioning from solar maximum conditions towards solar minimum.

Shuttle radiation dose measurements in the International Space Station orbits

NASA Technical Reports Server (NTRS)

Badhwar, Gautam D.

2002-01-01

The International Space Station (ISS) is now a reality with the start of a permanent human presence on board. Radiation presents a serious risk to the health and safety of the astronauts, and there is a clear requirement for estimating their exposures prior to and after flights. Predictions of the dose rate at times other than solar minimum or solar maximum have not been possible, because there has been no method to calculate the trapped-particle spectrum at intermediate times. Over the last few years, a tissue-equivalent proportional counter (TEPC) has been flown at a fixed mid-deck location on board the Space Shuttle in 51.65 degrees inclination flights. These flights have provided data that cover the expected changes in the dose rates due to changes in altitude and changes in solar activity from the solar minimum to the solar maximum of the current 23rd solar cycle. Based on these data, a simple function of the solar deceleration potential has been derived that can be used to predict the galactic cosmic radiation (GCR) dose rates to within +/-10%. For altitudes to be covered by the ISS, the dose rate due to the trapped particles is found to be a power-law function, rho(-2/3), of the atmospheric density, rho. This relationship can be used to predict trapped dose rates inside these spacecraft to +/-10% throughout the solar cycle. Thus, given the shielding distribution for a location inside the Space Shuttle or inside an ISS module, this approach can be used to predict the combined GCR + trapped dose rate to better than +/-15% for quiet solar conditions.

Subjective and physiological effects, and expired carbon monoxide concentrations in frequent and occasional cannabis smokers following smoked, vaporized, and oral cannabis administration.

PubMed

Newmeyer, Matthew N; Swortwood, Madeleine J; Abulseoud, Osama A; Huestis, Marilyn A

2017-06-01

Although smoking is the most common cannabis administration route, vaporization and consumption of cannabis edibles are common. Few studies directly compare cannabis' subjective and physiological effects following multiple administration routes. Subjective and physiological effects, and expired carbon monoxide (CO) were evaluated in frequent and occasional cannabis users following placebo (0.001% Δ 9 -tetrahydrocannabinol [THC]), smoked, vaporized, and oral cannabis (6.9% THC, ∼54mg). Participants' subjective ratings were significantly elevated compared to placebo after smoking and vaporization, while only occasional smokers' ratings were significantly elevated compared to placebo after oral dosing. Frequent smokers' maximum ratings were significantly different between inhaled and oral routes, while no differences in occasional smokers' maximum ratings between active routes were observed. Additionally, heart rate increases above baseline 0.5h after smoking (mean 12.2bpm) and vaporization (10.7bpm), and at 1.5h (13.0bpm) and 3h (10.2bpm) after oral dosing were significantly greater than changes after placebo, with no differences between frequent and occasional smokers. Finally, smoking produced significantly increased expired CO concentrations 0.25-6h post-dose compared to vaporization. All participants had significant elevations in subjective effects after smoking and vaporization, but only occasional smokers after oral cannabis, indicating partial tolerance to subjective effects with frequent exposure. There were no differences in occasional smokers' maximum subjective ratings across the three active administration routes. Vaporized cannabis is an attractive alternative for medicinal administrations over smoking or oral routes; effects occur quickly and doses can be titrated with minimal CO exposure. These results have strong implications for safety and abuse liability assessments. Published by Elsevier B.V.

Metabolism of isotretinoin. Biliary excretion of isotretinoin glucuronide in the rat.

PubMed

Meloche, S; Besner, J G

1986-01-01

The biliary metabolites of isotretinoin were examined after iv administration of 4-20-mg/kg doses to vitamin A-normal bile duct-cannulated rats. Analysis of bile by reverse phase high performance liquid chromatography showed that injection of isotretinoin is followed by a rapid excretion of metabolites in bile. Isotretinoin glucuronide was identified as the major metabolite in bile. A specific high performance liquid chromatography method based on the assay of generated isotretinoin in beta-glucuronidase-treated bile was developed for the determination of isotretinoin glucuronide in bile samples. The excretion rate of isotretinoin glucuronide increased rapidly to reach a maximum 55 min after dosing and then declined exponentially. After 330 min of collection, biliary excretion of isotretinoin glucuronide was almost complete, and the metabolite accounted for 34.8-37.9% of the dose. These results indicate that conjugation with glucuronic acid represents a major pathway for the metabolism of pharmacological doses of isotretinoin. The maximum excretion rate of isotretinoin glucuronide in bile increased in a linear manner with the dose of isotretinoin, and no delay was observed after the larger doses. These data suggest that glucuronidation and biliary excretion are not saturated at high pharmacological doses of isotretinoin.

Microbial endogenous response to acute inhibitory impact of antibiotics.

PubMed

Pala-Ozkok, I; Kor-Bicakci, G; Çokgör, E U; Jonas, D; Orhon, D

2017-06-13

Enhanced endogenous respiration was observed as the significant/main response of the aerobic microbial culture under pulse exposure to antibiotics: sulfamethoxazole, tetracycline and erythromycin. Peptone mixture and acetate were selected as organic substrates to compare the effect of complex and simple substrates. Experiments were conducted with microbial cultures acclimated to different sludge ages of 10 and 2 days, to visualize the effect of culture history. Evaluation relied on modeling of oxygen uptake rate profiles, reflecting the effect of all biochemical reactions associated with substrate utilization. Model calibration exhibited significant increase in values of endogenous respiration rate coefficient with all antibiotic doses. Enhancement of endogenous respiration was different with antibiotic type and initial dose. Results showed that both peptone mixture and acetate cultures harbored resistance genes against the tested antibiotics, which suggests that biomass spends cellular maintenance energy for activating the required antibiotic resistance mechanisms to survive, supporting higher endogenous decay rates. [Formula: see text]: maximum growth rate for X H (day -1 ); K S : half saturation constant for growth of X H (mg COD/L); b H : endogenous decay rate for X H (day -1 ); k h : maximum hydrolysis rate for S H1 (day -1 ); K X : hydrolysis half saturation constant for S H1 (mg COD/L); k hx : maximum hydrolysis rate for X S1 (day -1 ); K XX : hydrolysis half saturation constant for X S1 (mg COD/L); k STO : maximum storage rate of PHA by X H (day -1 ); [Formula: see text]: maximum growth rate on PHA for X H (day -1 ); K STO : half saturation constant for storage of PHA by X H (mg COD/L); X H1 : initial active biomass (mg COD/L).

Commissioning dosimetry and in situ dose mapping of a semi-industrial Cobalt-60 gamma-irradiation facility using Fricke and Ceric-cerous dosimetry system and comparison with Monte Carlo simulation data

NASA Astrophysics Data System (ADS)

Mortuza, Md Firoz; Lepore, Luigi; Khedkar, Kalpana; Thangam, Saravanan; Nahar, Arifatun; Jamil, Hossen Mohammad; Bandi, Laxminarayan; Alam, Md Khorshed

2018-03-01

Characterization of a 90 kCi (3330 TBq), semi-industrial, cobalt-60 gamma irradiator was performed by commissioning dosimetry and in-situ dose mapping experiments with Ceric-cerous and Fricke dosimetry systems. Commissioning dosimetry was carried out to determine dose distribution pattern of absorbed dose in the irradiation cell and products. To determine maximum and minimum absorbed dose, overdose ratio and dwell time of the tote boxes, homogeneous dummy product (rice husk) with a bulk density of 0.13 g/cm3 were used in the box positions of irradiation chamber. The regions of minimum absorbed dose of the tote boxes were observed in the lower zones of middle plane and maximum absorbed doses were found in the middle position of front plane. Moreover, as a part of dose mapping, dose rates in the wall positions and some selective strategic positions were also measured to carry out multiple irradiation program simultaneously, especially for low dose research irradiation program. In most of the cases, Monte Carlo simulation data, using Monte Carlo N-Particle eXtended code version MCNPX 2.7., were found to be in congruence with experimental values obtained from Ceric-cerous and Fricke dosimetry; however, in close proximity positions from the source, the dose rate variation between chemical dosimetry and MCNP was higher than distant positions.

RadNuc: A graphical user interface to deliver dose rate patterns encountered in nuclear medicine with a 137Cs irradiator

PubMed Central

Pasternack, Jordan B.; Howell, Roger W.

2012-01-01

The temporal variations in absorbed dose rates to organs and tissues in the body are very large in diagnostic and therapeutic nuclear medicine. The response of biological endpoints of relevance to radiation safety and therapeutic efficacy are generally modulated by dose rate. Therefore, it is important to understand how the complex dose rate patterns encountered in nuclear medicine impact relevant biological responses. Accordingly, a graphical user interface (GUI) was created to control a cesium-137 irradiator to deliver such dose rate patterns. Methods Visual Basic 6.0 was used to create a user-friendly GUI to control the dose rate by varying the thickness of a mercury attenuator. The GUI facilitates the delivery of a number of dose rate patterns including constant, exponential increase or decrease, and multi-component exponential. Extensive visual feedback is provided by the GUI during both the planning and delivery stages. Results The GUI controlled irradiator can achieve a maximum dose rate of 40 cGy/hr and a minimum dose rate of 0.01 cGy/hr. Addition of machined lead blocks can be used to further reduce the minimum dose rate to 0.0001 cGy/hr. Measured dose rate patterns differed from programmed dose rate patterns in total dose by 3.2% to 8.4%. Conclusion The GUI controlled irradiator is able to accurately create dose rate patterns encountered in nuclear medicine and other related fields. This makes it an invaluable tool for studying the effects of chronic constant and variable low dose rates on biological tissues in the contexts of both radiation protection and clinical administration of internal radionuclides. PMID:23265668

RadNuc: a graphical user interface to deliver dose rate patterns encountered in nuclear medicine with a 137Cs irradiator.

PubMed

Pasternack, Jordan B; Howell, Roger W

2013-02-01

The temporal variations in absorbed dose rates to organs and tissues in the body are very large in diagnostic and therapeutic nuclear medicine. The response of biological endpoints of relevance to radiation safety and therapeutic efficacy is generally modulated by dose rate. Therefore, it is important to understand how the complex dose rate patterns encountered in nuclear medicine impact relevant biological responses. Accordingly, a graphical user interface (GUI) was created to control a cesium-137 irradiator to deliver such dose rate patterns. Visual Basic 6.0 was used to create a user-friendly GUI to control the dose rate by varying the thickness of a mercury attenuator. The GUI facilitates the delivery of a number of dose rate patterns including constant, exponential increase or decrease, and multi-component exponential. Extensive visual feedback is provided by the GUI during both the planning and delivery stages. The GUI controlled irradiator can achieve a maximum dose rate of 40 cGy/h and a minimum dose rate of 0.01 cGy/h. Addition of machined lead blocks can be used to further reduce the minimum dose rate to 0.0001 cGy/h. Measured dose rate patterns differed from programmed dose rate patterns in total dose by 3.2% to 8.4%. The GUI controlled irradiator is able to accurately create dose rate patterns encountered in nuclear medicine and other related fields. This makes it an invaluable tool for studying the effects of chronic constant and variable low dose rates on biological tissues in the contexts of both radiation protection and clinical administration of internal radionuclides. Copyright © 2013 Elsevier Inc. All rights reserved.

Eltoprazine counteracts l-DOPA-induced dyskinesias in Parkinson’s disease: a dose-finding study

PubMed Central

Rosenblad, Carl; af Edholm Arvidsson, Karolina; Wictorin, Klas; Keywood, Charlotte; Shankar, Bavani; Lowe, David A.; Björklund, Anders; Widner, Håkan

2015-01-01

In advanced stages of Parkinson’s disease, serotonergic terminals take up l-DOPA and convert it to dopamine. Abnormally released dopamine may participate in the development of l-DOPA-induced dyskinesias. Simultaneous activation of 5-HT1A and 5-HT1B receptors effectively blocks l-DOPA-induced dyskinesias in animal models of dopamine depletion, justifying a clinical study with eltoprazine, a 5-HT1A/B receptor agonist, against l-DOPA-induced dyskinesias in patients with Parkinson’s disease. A double-blind, randomized, placebo-controlled and dose-finding phase I/IIa study was conducted. Single oral treatment with placebo or eltoprazine, at 2.5, 5 and 7.5 mg, was tested in combination with a suprathreshold dose of l-DOPA (Sinemet®) in 22 patients with Parkinson’s disease (16 male/six female; 66.6 ± 8.8 years old) with l-DOPA-induced dyskinesias. A Wilcoxon Signed Ranked Test was used to compare each eltoprazine dose level to paired randomized placebo on the prespecified primary efficacy variables; area under the curve scores on Clinical Dyskinesia Rating Scale for 3 h post-dose and maximum change of Unified Parkinson’s Disease Rating Scale part III for 3 h post-dose. Secondary objectives included effects on maximum Clinical Dyskinesia Rating Scale score, area under the curve of Rush Dyskinesia Rating Scale score for 3 h post-dose, mood parameters measured by Hospital Anxiety Depression Scale and Montgomery Asberg Depression Rating Scale along with the pharmacokinetics, safety and tolerability profile of eltoprazine. A mixed model repeated measures was used for post hoc analyses of the area under the curve and peak Clinical Dyskinesia Rating Scale scores. It was found that serum concentrations of eltoprazine increased in a dose-proportional manner. Following levodopa challenge, 5 mg eltoprazine caused a significant reduction of l-DOPA-induced dyskinesias on area under the curves of Clinical Dyskinesia Rating Scale [–1.02(1.49); P = 0.004] and Rush Dyskinesia Rating Scale [–0.15(0.23); P = 0.003]; and maximum Clinical Dyskinesia Rating Scale score [–1.14(1.59); P = 0.005]. The post hoc analysis confirmed these results and also showed an antidyskinetic effect of 7.5 mg eltoprazine. Unified Parkinson’s Disease Rating Scale part III scores did not differ between the placebo and eltoprazine treatments. The most frequent adverse effects after eltoprazine were nausea and dizziness. It can be concluded that a single dose, oral treatment with eltoprazine has beneficial antidyskinetic effects without altering normal motor responses to l-DOPA. All doses of eltoprazine were well tolerated, with no major adverse effects. Eltoprazine has a favourable risk-benefit and pharmacokinetic profile in patients with Parkinson’s disease. The data support further clinical studies with chronic oral eltoprazine to treat l-DOPA-induced-dyskinesias. PMID:25669730

Conditioning of the 4 Curies Radium-226 Sealed Radiation Source in Thailand

DOE Office of Scientific and Technical Information (OSTI.GOV)

Punnachaiya, M.; Sawangsri, T.; Wanabongse, P.

This paper describes the conditioning of the 4 curies Radium-226 (Ra-226) sealed radiation source using as a teletherapy unit for cancer treatment in Thailand. The conditioning was under the International Atomic Energy Agency (IAEA) supervision and budgetary supports, comprised of 6 operational steps: the surface dose rate and actual dimension of radium unit measurements, the appropriate lead shielding design with IAEA approval, confirmation of radioactive contamination before conditioning (smear test and radon gas leakage test), transfer of radium source unit into the designed shielding, confirmation of radioactive contamination and dose rate measurement after conditioning, and transportation of Ra-226 conditioning wastemore » package to OAP interim waste storage. The Ra-226 unit was taken out of OAP temporary waste storage for the surface dose rate and the actual dimension measurements behind the 12 inches thick heavy concrete shielding. The maximum measured surface dose rate was 70 R/hr. The special lead container was designed according to its surface dose rate along the source unit which the maximum permissible dose limit for surface dose rate of waste package after conditioning at 2 mSv/hr was applied. The IAEA approved container had total weight of 2.4 ton. After the confirmation of radioactive contamination, Ra-226 source unit was transferred and loaded in the designed lead shielding within 2 minutes. The results of smear test before and after conditioning including radon gas leakage test revealed that there was no radioactive contamination. After conditioning, the surface dose rate measured on the top, bottom were 15,10 mR/hr and varied from 6 - 50 mR/hr around lead container. The Ra-226 conditioning waste package was safely transported to store in OAP interim waste storage. Total working time including the time consumed for radon gas leakage test was 3.5 hours. The total radiation dose received by 16 operators, were ranged from 1 - 69.84 {mu}Sv and the operational team completed the conditioning safely within the effective dose limit for occupational exposure of 50 mSv/year (200 {mu}Sv/day). (authors)« less

Probabilistic dose assessment of normal operations and accident conditions for an assured isolation facility in Texas

NASA Astrophysics Data System (ADS)

Arno, Matthew Gordon

Texas is investigating building a long-term waste storage facility, also known as an Assured Isolation Facility. This is an above-ground low-level radioactive waste storage facility that is actively maintained and from which waste may be retrieved. A preliminary, scoping-level analysis has been extended to consider more complex scenarios of radiation streaming and skyshine by using the computer code Monte Carlo N-Particle (MCNP) to model the facility in greater detail. Accidental release scenarios have been studied in more depth to better assess the potential dose to off-site individuals. Using bounding source term assumptions, the projected radiation doses and dose rates are estimated to exceed applicable limits by an order of magnitude. By altering the facility design to fill in the hollow cores of the prefabricated concrete slabs used in the roof over the "high-gamma rooms," where the waste with the highest concentration of gamma emitting radioactive material is stored, dose rates outside the facility decrease by an order of magnitude. With the modified design, the annual dose at the site fenceline is estimated at 86 mrem, below the 100 mrem annual limit for exposure of the public. Within the site perimeter, the dose rates are lowered sufficiently such that it is not necessary to categorize many workers and contractor personnel as radiation workers, saving on costs as well as being advisable under ALARA principles. A detailed analysis of bounding accidents incorporating information on the local meteorological conditions indicate that the maximum committed effective dose equivalent from the passage of a plume of material released in an accident at any of the cities near the facility is 59 :rem in the city of Eunice, NM based on the combined day and night meteorological conditions. Using the daytime meteorological conditions, the maximum dose at any city is 7 :rem, also in the city of Eunice. The maximum dose at the site boundary was determined to be 230 mrem using the combined day and night meteorological conditions and 33 mrem using the daytime conditions.

Thermal limits on MV x-ray production by bremsstrahlung targets in the context of novel linear accelerators.

PubMed

Wang, Jinghui; Trovati, Stefania; Borchard, Philipp M; Loo, Billy W; Maxim, Peter G; Fahrig, Rebecca

2017-12-01

To study the impact of target geometrical and linac operational parameters, such as target material and thickness, electron beam size, repetition rate, and mean current on the ability of the radiotherapy treatment head to deliver high-dose-rate x-ray irradiation in the context of novel linear accelerators capable of higher repetition rates/duty cycle than conventional clinical linacs. The depth dose in a water phantom without a flattening filter and heat deposition in an x-ray target by 10 MeV pulsed electron beams were calculated using the Monte-Carlo code MCNPX, and the transient temperature behavior of the target was simulated by ANSYS. Several parameters that affect both the dose distribution and temperature behavior were investigated. The target was tungsten with a thickness ranging from 0 to 3 mm and a copper heat remover layer. An electron beam with full width at half maximum (FWHM) between 0 and3 mm and mean current of 0.05-2 mA was used as the primary beam at repetition rates of 100, 200, 400, and 800 Hz. For a 10 MeV electron beam with FWHM of 1 mm, pulse length of 5 μs, by using a thin tungsten target with thickness of 0.2 mm instead of 1 mm, and by employing a high repetition rate of 800 Hz instead of 100 Hz, the maximum dose rate delivered can increase two times from 0.57 to 1.16 Gy/s. In this simple model, the limiting factor on dose rate is the copper heat remover's softening temperature, which was considered to be 500°C in our study. A high dose rate can be obtained by employing thin targets together with high repetition rate electron beams enabled by novel linac designs, whereas the benefit of thin targets is marginal at conventional repetition rates. Next generation linacs used to increase dose rate need different target designs compared to conventional linacs. © 2017 American Association of Physicists in Medicine.

Spacecraft shielding for a Mars mission

NASA Astrophysics Data System (ADS)

O'Brien, K.

Calculations of the effective radiation dose due to cosmic rays in the interplanetary medium between Earth and Mars show that, as in the atmosphere above the Pfotzer Maximum, the dose rate increases with increasing wall thickness. An unshielded space crew member would receive almost 70 rem (0.70 Sv) a year. The effect of a typically proposed composite space-craft hull of aluminum and polyethylene would increase the dose rate by a few percent. However, 100 g/cm2 of almost any light material would more than double the cosmic radiation exposure of the crew.

MAGIC with formaldehyde applied to dosimetry of HDR brachytherapy source

NASA Astrophysics Data System (ADS)

Marques; T; Fernandes; J; Barbi; G; Nicolucci; P; Baffa; O

2009-05-01

The use of polymer gel dosimeters in brachytherapy can allow the determination of three-dimensional dose distributions in large volumes and with high spatial resolution if an adequate calibration process is performed. One of the major issues in these experiments is the polymer gel response dependence on dose rate when high dose rate sources are used and the doses in the vicinity of the sources are to be determinated. In this study, the response of a modified MAGIC polymer gel with formaldehyde around an Iridium-192 HDR brachytherapy source is presented. Experimental results obtained with this polymer gel were compared with ionization chamber measurements and with Monte Carlo simulation with PENELOPE. A maximum difference of 3.10% was found between gel dose measurements and Monte Carlo simulation at a radial distance of 18 mm from the source. The results obtained show that the gel's response is strongly influenced by dose rate and that a different calibration should be used for the vicinity of the source and for regions of lower dose rates. The results obtained in this study show that, provided the proper calibration is performed, MAGIC with formaldehyde can be successfully used to accurate determinate dose distributions form high dose rate brachytherapy sources.

Radiation hardness study of semi-insulating GaAs detectors against 5 MeV electrons

NASA Astrophysics Data System (ADS)

Šagátová, A.; Zaťko, B.; Nečas, V.; Sedlačková, K.; Boháček, P.; Fülöp, M.; Pavlovič, M.

2018-01-01

A radiation hardness study of Semi-Insulating (SI) GaAs detectors against 5 MeV electrons is described in this paper. The influence of two parameters, the accumulative absorbed dose (from 1 to 200 kGy) and the applied dose rate (20, 40 or 80 kGy/h), on detector spectrometric properties were studied. The accumulative dose has influenced all evaluated spectrometric properties and also negatively affected the detector CCE (Charge Collection Efficiency). We have observed its systematic reduction from an initial 79% before irradiation down to about 51% at maximum dose of 200 kGy. Relative energy resolution was also influenced by electron irradiation. Its degradation was obvious in the range of doses from 24 up to a maximum dose of 200 kGy, where an increase from 19% up to 31% at 200 V reverse voltage was noticed. On the other hand, a global increase of detection efficiency with accumulative absorbed dose was observed for all samples. Concerning the actual detector degradation we can assume that the tested SI GaAs detectors will be able to operate up to a dose of 300 kGy at least, when irradiated by 5 MeV electrons. The second investigated parameter of irradiation, the dose rate of chosen ranges, did not greatly alter the spectrometric properties of studied detectors.

A retrospective analysis of rectal and bladder dose for gynecological brachytherapy treatments with GZP6 HDR afterloading system.

PubMed

Bahreyni Toossi, Mohammad Taghi; Ghorbani, Mahdi; Makhdoumi, Yasha; Taheri, Mojtaba; Homaee Shandiz, Fatemeh; Zahed Anaraki, Siavash; Soleimani Meigooni, Ali

2012-01-01

The aim of this work is to evaluate rectal and bladder dose for the patients treated for gynecological cancers. The GZP6 high dose rate brachytherapy system has been recently introduced to a number of radiation therapy departments in Iran, for treatment of various tumor sites such as cervix and vagina. Our analysis was based on dose measurements for 40 insertions in 28 patients, treated by a GZP6 unit between June 2009 and November 2010. Treatments consisted of combined teletherapy and intracavitary brachytherapy. In vivo dosimetry was performed with TLD-400 chips and TLD-100 microcubes in the rectum and bladder. The average of maximum rectal and bladder dose values were found to be 7.62 Gy (range 1.72-18.55 Gy) and 5.17 Gy (range 0.72-15.85 Gy), respectively. It has been recommended by the ICRU that the maximum dose to the rectum and bladder in intracavitary treatment of vaginal or cervical cancer should be lower than 80% of the prescribed dose to point A in the Manchester system. In this study, of the total number of 40 insertions, maximum rectal dose in 29 insertions (72.5% of treatment sessions) and maximum bladder dose in 18 insertions (45% of treatments sessions) were higher than 80% of the prescribed dose to the point of dose prescription. In vivo dosimetry for patients undergoing treatment by GZP6 brachytherapy system can be used for evaluation of the quality of brachytherapy treatments by this system. This information could be used as a base for developing the strategy for treatment of patients treated with GZP6 system.

A retrospective analysis of rectal and bladder dose for gynecological brachytherapy treatments with GZP6 HDR afterloading system

PubMed Central

Bahreyni Toossi, Mohammad Taghi; Ghorbani, Mahdi; Makhdoumi, Yasha; Taheri, Mojtaba; Homaee Shandiz, Fatemeh; Zahed Anaraki, Siavash; Soleimani Meigooni, Ali

2012-01-01

Aim The aim of this work is to evaluate rectal and bladder dose for the patients treated for gynecological cancers. Background The GZP6 high dose rate brachytherapy system has been recently introduced to a number of radiation therapy departments in Iran, for treatment of various tumor sites such as cervix and vagina. Materials and methods Our analysis was based on dose measurements for 40 insertions in 28 patients, treated by a GZP6 unit between June 2009 and November 2010. Treatments consisted of combined teletherapy and intracavitary brachytherapy. In vivo dosimetry was performed with TLD-400 chips and TLD-100 microcubes in the rectum and bladder. Results The average of maximum rectal and bladder dose values were found to be 7.62 Gy (range 1.72–18.55 Gy) and 5.17 Gy (range 0.72–15.85 Gy), respectively. It has been recommended by the ICRU that the maximum dose to the rectum and bladder in intracavitary treatment of vaginal or cervical cancer should be lower than 80% of the prescribed dose to point A in the Manchester system. In this study, of the total number of 40 insertions, maximum rectal dose in 29 insertions (72.5% of treatment sessions) and maximum bladder dose in 18 insertions (45% of treatments sessions) were higher than 80% of the prescribed dose to the point of dose prescription. Conclusion In vivo dosimetry for patients undergoing treatment by GZP6 brachytherapy system can be used for evaluation of the quality of brachytherapy treatments by this system. This information could be used as a base for developing the strategy for treatment of patients treated with GZP6 system. PMID:24377037

Role of step size and max dwell time in anatomy based inverse optimization for prostate implants

PubMed Central

Manikandan, Arjunan; Sarkar, Biplab; Rajendran, Vivek Thirupathur; King, Paul R.; Sresty, N.V. Madhusudhana; Holla, Ragavendra; Kotur, Sachin; Nadendla, Sujatha

2013-01-01

In high dose rate (HDR) brachytherapy, the source dwell times and dwell positions are vital parameters in achieving a desirable implant dose distribution. Inverse treatment planning requires an optimal choice of these parameters to achieve the desired target coverage with the lowest achievable dose to the organs at risk (OAR). This study was designed to evaluate the optimum source step size and maximum source dwell time for prostate brachytherapy implants using an Ir-192 source. In total, one hundred inverse treatment plans were generated for the four patients included in this study. Twenty-five treatment plans were created for each patient by varying the step size and maximum source dwell time during anatomy-based, inverse-planned optimization. Other relevant treatment planning parameters were kept constant, including the dose constraints and source dwell positions. Each plan was evaluated for target coverage, urethral and rectal dose sparing, treatment time, relative target dose homogeneity, and nonuniformity ratio. The plans with 0.5 cm step size were seen to have clinically acceptable tumor coverage, minimal normal structure doses, and minimum treatment time as compared with the other step sizes. The target coverage for this step size is 87% of the prescription dose, while the urethral and maximum rectal doses were 107.3 and 68.7%, respectively. No appreciable difference in plan quality was observed with variation in maximum source dwell time. The step size plays a significant role in plan optimization for prostate implants. Our study supports use of a 0.5 cm step size for prostate implants. PMID:24049323

SU-F-T-301: Planar Dose Pass Rate Inflation Due to the MapCHECK Measurement Uncertainty Function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bailey, D; Spaans, J; Kumaraswamy, L

Purpose: To quantify the effect of the Measurement Uncertainty function on planar dosimetry pass rates, as analyzed with Sun Nuclear Corporation analytic software (“MapCHECK” or “SNC Patient”). This optional function is toggled on by default upon software installation, and automatically increases the user-defined dose percent difference (%Diff) tolerance for each planar dose comparison. Methods: Dose planes from 109 IMRT fields and 40 VMAT arcs were measured with the MapCHECK 2 diode array, and compared to calculated planes from a commercial treatment planning system. Pass rates were calculated within the SNC analytic software using varying calculation parameters, including Measurement Uncertainty onmore » and off. By varying the %Diff criterion for each dose comparison performed with Measurement Uncertainty turned off, an effective %Diff criterion was defined for each field/arc corresponding to the pass rate achieved with MapCHECK Uncertainty turned on. Results: For 3%/3mm analysis, the Measurement Uncertainty function increases the user-defined %Diff by 0.8–1.1% average, depending on plan type and calculation technique, for an average pass rate increase of 1.0–3.5% (maximum +8.7%). For 2%, 2 mm analysis, the Measurement Uncertainty function increases the user-defined %Diff by 0.7–1.2% average, for an average pass rate increase of 3.5–8.1% (maximum +14.2%). The largest increases in pass rate are generally seen with poorly-matched planar dose comparisons; the MapCHECK Uncertainty effect is markedly smaller as pass rates approach 100%. Conclusion: The Measurement Uncertainty function may substantially inflate planar dose comparison pass rates for typical IMRT and VMAT planes. The types of uncertainties incorporated into the function (and their associated quantitative estimates) as described in the software user’s manual may not accurately estimate realistic measurement uncertainty for the user’s measurement conditions. Pass rates listed in published reports or otherwise compared to the results of other users or vendors should clearly indicate whether the Measurement Uncertainty function is used.« less

External beam boost versus interstitial high-dose-rate brachytherapy boost in the adjuvant radiotherapy following breast-conserving therapy in early-stage breast cancer: a dosimetric comparison

PubMed Central

Melchert, Corinna; Kovács, György

2016-01-01

Purpose This study aims to compare the dosimetric data of local tumor's bed dose escalation (boost) with photon beams (external beam radiation therapy – EBRT) versus high-dose-rate interstitial brachytherapy (HDR-BT) after breast-conserving treatment in women with early-stage breast cancer. Material and methods We analyzed the treatment planning data of 136 irradiated patients, treated between 2006 and 2013, who underwent breast-conserving surgery and adjuvant whole breast irradiation (WBI; 50.4 Gy) and boost (HDR-BT: 10 Gy in one fraction [n = 36]; EBRT: 10 Gy in five fractions [n = 100]). Organs at risk (OAR; heart, ipsilateral lung, skin, most exposed rib segment) were delineated. Dosimetric parameters were calculated with the aid of dose-volume histograms (DVH). A non-parametric test was performed to compare the two different boost forms. Results There was no difference for left-sided cancers regarding the maximum dose to the heart (HDR-BT 29.8% vs. EBRT 29.95%, p = 0.34). The maximum doses to the other OAR were significantly lower for HDR-BT (Dmax lung 47.12% vs. 87.7%, p < 0.01; rib 61.17% vs. 98.5%, p < 0.01; skin 57.1% vs. 94.75%, p < 0.01; in the case of right-sided breast irradiation, dose of the heart 6.00% vs. 16.75%, p < 0.01). Conclusions Compared to EBRT, local dose escalation with HDR-BT presented a significant dose reduction to the investigated OAR. Only left-sided irradiation showed no difference regarding the maximum dose to the heart. Reducing irradiation exposure to OAR could result in a reduction of long-term side effects. Therefore, from a dosimetric point of view, an interstitial boost complementary to WBI via EBRT seems to be more advantageous in the adjuvant radiotherapy of breast cancer. PMID:27648082

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, C; Lin, M; Chen, L

Purpose: Recent in vitro and in vivo experimental findings provided strong evidence that pulsed low-dose-rate radiotherapy (PLDR) produced equivalent tumor control as conventional radiotherapy with significantly reduced normal tissue toxicities. This work aimed to implement a PLDR clinical protocol for the management of recurrent cancers utilizing IMRT and VMAT. Methods: Our PLDR protocol requires that the daily 2Gy dose be delivered in 0.2Gy×10 pulses with a 3min interval between the pulses. To take advantage of low-dose hyper-radiosensitivity the mean dose to the target is set at 0.2Gy and the maximum dose is limited to 0.4Gy per pulse. Practical planning strategiesmore » were developed for IMRT and VMAT: (1) set 10 ports for IMRT and 10 arcs for VMAT with each angle/arc as a pulse; (2) set the mean dose (0.2Gy) and maximum dose (0.4Gy) to the target per pulse as hard constraints (no constraints to OARs); (3) select optimal port/arc angles to avoid OARs; and (4) use reference structures in or around target/OARs to reduce maximum dose to the target/OARs. IMRT, VMAT and 3DCRT plans were generated for 60 H and N, breast, lung, pancreas and prostate patients and compared. Results: All PLDR treatment plans using IMRT and VMAT met the dosimetry requirements of the PLDR protocol (mean target dose: 0.20Gy±0.01Gy; maximum target dose < 0.4Gy). In comparison with 3DCRT, IMRT and VMAT exhibited improved target dose conformity and OAR dose sparing. A single arc can minimize the difference in the target dose due to multi-angle incidence although the delivery time is longer than 3DCRT and IMRT. Conclusion: IMRT and VMAT are better modalities for PLDR treatment of recurrent cancers with superior target dose conformity and critical structure sparing. The planning strategies/guidelines developed in this work are practical for IMRT/VMAT treatment planning to meet the dosimetry requirements of the PLDR protocol.« less

Pre-operative combined 5-FU, low dose leucovorin, and sequential radiation therapy for unresectable rectal cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Minsky, B.D.; Cohen, A.M.; Kemeny, N.

1993-04-02

The authors performed a Phase 1 trial to determine the maximum tolerated dose of combined pre-operative radiation (5040 cGy) and 2 cycles (bolus daily [times] 5) of 5-FU and low dose LV (20 mg/m2), followed by surgery and 10 cycles of post-operative LV/5-FU in patients with unresectable primary or recurrent rectal cancer. Twelve patients were entered. The initial dose of 5-FU was 325 mg/m2. 5-FU was to be escalated while the LV remained constant at 20 mg/m2. Chemotherapy began on day 1 and radiation on day 8. The post-operative chemotherapy was not dose escalated; 5-FU: 425 mg/m2 and LV: 20more » mg/m2. The median follow-up was 14 months (7--16 months). Following pre-operative therapy, the resectability rate with negative margins was 91% and the pathologic complete response rate was 9%. For the combined modality segment (preoperative) the incidence of any grade 3+ toxicity was diarrhea: 17%, dysuria: 8%, mucositis: 8%, and erythema: 8%. The median nadir counts were WBC: 3.1, HGB: 8.8, and PLT: 153000. The maximum tolerated dose of 5-FU for pre-operative combined LV/5-FU/RT was 325 mg/m2 with no escalation possible. Therefore, the recommended dose was less than 325 mg/m2. Since adequate doses of 5-FU to treat systemic disease could not be delivered until at least 3 months (cycle 3) following the start of therapy, the authors do not recommend that this 5-FU, low dose LV, and sequential radiation therapy regimen be used as presently designed. However, given the 91% resectability rate they remain encouraged with this approach. 31 refs., 1 fig., 2 tabs.« less

Targeting MRS-Defined Dominant Intraprostatic Lesions with Inverse-Planned High Dose Rate Brachytherapy

DTIC Science & Technology

2007-02-01

bladder and the rectum are overprotected while the PTV coverage is undesirably reduced. On the other hand, if their maximum dose is increased and/or...B, the bladder and rectum were overprotected with undesirably low PTV coverage (84.54%). The reduction of their weighting factor increased PTV

Concentration dependence of biotransformation in fish liver S9: Optimizing substrate concentrations to estimate hepatic clearance for bioaccumulation assessment.

PubMed

Lo, Justin C; Allard, Gayatri N; Otton, S Victoria; Campbell, David A; Gobas, Frank A P C

2015-12-01

In vitro bioassays to estimate biotransformation rate constants of contaminants in fish are currently being investigated to improve bioaccumulation assessments of hydrophobic contaminants. The present study investigates the relationship between chemical substrate concentration and in vitro biotransformation rate of 4 environmental contaminants (9-methylanthracene, pyrene, chrysene, and benzo[a]pyrene) in rainbow trout (Oncorhynchus mykiss) liver S9 fractions and methods to determine maximum first-order biotransformation rate constants. Substrate depletion experiments using a series of initial substrate concentrations showed that in vitro biotransformation rates exhibit strong concentration dependence, consistent with a Michaelis-Menten kinetic model. The results indicate that depletion rate constants measured at initial substrate concentrations of 1 μM (a current convention) could underestimate the in vitro biotransformation potential and may cause bioconcentration factors to be overestimated if in vitro biotransformation rates are used to assess bioconcentration factors in fish. Depletion rate constants measured using thin-film sorbent dosing experiments were not statistically different from the maximum depletion rate constants derived using a series of solvent delivery-based depletion experiments for 3 of the 4 test chemicals. Multiple solvent delivery-based depletion experiments at a range of initial concentrations are recommended for determining the concentration dependence of in vitro biotransformation rates in fish liver fractions, whereas a single sorbent phase dosing experiment may be able to provide reasonable approximations of maximum depletion rates of very hydrophobic substances. © 2015 SETAC.

Natural and anthropogenic radionuclides in rocks and beach sands from Ezine region (Canakkale), Western Anatolia, Turkey.

PubMed

Orgün, Y; Altinsoy, N; Sahin, S Y; Güngör, Y; Gültekin, A H; Karahan, G; Karacik, Z

2007-06-01

This paper represents the first reports on the natural and anthropogenic radionuclides in Kestanbol granitic pluton and surrounding rocks, and coastal region of the Ezine town. To assess the radiological hazard of the natural radioactivity, the radium equivalent activity, the absorbed dose rate and the external hazard index were calculated, and in situ gamma dose rates were measured. The high-activity concentrations were measured in the pluton and sands, which was originated mainly from the pluton, due to the presence of zircon, allanite, monazite, thorite, uranothorite and apatite. The average activity concentrations of (238)U, (232)Th and (40)K are 174.78, 204.69 and 1171.95 Bq kg(-1) for pluton, and 290.36, 532.04 and 1160.75 Bq kg(-1) for sands, respectively. (137)Cs in Ezine region ranged from 0-6.57 Bq kg(-1). The average absorbed dose rate for the granitic and sand samples were calculated to be 251.6 and 527.92 nGy h(-1), respectively. The maximum contribution to the total absorbed gamma dose rate in air was due to the (232)Th (52.3% for pluton and 67.1% for sands). The Raeq activities of the pluton and sands are higher than the recommended maximum value of 370 Bq kg(-1) criterion limit of Raeq activity for building materials.

Stomatal and non-stomatal factors regulated the photosynthesis of soybean seedlings in the present of exogenous bisphenol A.

PubMed

Jiao, Liya; Wang, Lihong; Zhou, Qing; Huang, Xiaohua

2017-11-01

Bisphenol A (BPA) is an emerging environmental endocrine disruptor that has toxic effects on plants growth. Photosynthesis supplies the substances and energy required for plant growth, and regulated by stomatal and non-stomatal factors. Therefore, in this study, to reveal how BPA affects photosynthesis in soybean seedlings (Glycine max L.) from the perspective of stomatal and non-stomatal factors, the stomatal factors (stomatal conductance and behaviours) and non-stomatal factors (Hill reaction, apparent quantum efficiency, Rubisco activity, carboxylation efficiency, the maximum Rubisco carboxylation velocity, ribulose-1,5-bisphospate regeneration capacities mediated by maximum electron transport rates, and triose phosphate utilization rate) were investigated using a portable photosynthesis system. Moreover, the pollution of BPA in the environment was simulated. The results indicate that low-dose BPA enhanced net photosynthetic rate (P n ) primarily by promoting stomatal factors, resulting in increased relative growth rates and accelerated soybean seedling growth. High-dose BPA decreases the P n by simultaneously inhibiting stomatal and non-stomatal factors, and this inhibition decreases the relative growth rates further reducing soybean seedling growth. Following the withdrawal of BPA, all of the indices were restored to varying degrees. In conclusion, low-dose BPA increased the P n by promoting stomatal factors while high-dose BPA decreased the P n by simultaneously inhibiting stomatal and non-stomatal factors. These findings provide a model (or, hypothesis) for the effects of BPA on plant photosynthesis. Copyright © 2017 Elsevier Inc. All rights reserved.

MO-F-CAMPUS-I-02: Occupational Conceptus Doses From Fluoroscopically-Guided Interventional Procedures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Damilakis, J; Perisinakis, K; Solomou, G

Purpose: The aim of this method was to provide dosimetric data on conceptus dose for the pregnant employee who participates in fluoroscopically-guided interventional procedures. Methods: Scattered air-kerma dose rates were obtained for 17 fluoroscopic projections involved in interventional procedures. These projections were simulated on an anthropomorphic phantom placed on the examination table supine. The operating theater was divided into two grids relative to the long table sides. Each grid consisted of 33 cells spaced 0.50 m apart. During the simulated exposures, at each cell, scatter air-kerma rate was measured at 110 cm from the floor i.e. at the height ofmore » the waist of the pregnant worker. Air-kerma rates were divided by the dose area product (DAP) rate of each exposure to obtain normalized data. For each projection, measurements were performed for 3 kVp and 3 filtration values i.e. for 9 different x-ray spectra. All measurements were performed by using a modern C-arm angiographic system (Siemens Axiom Artis, Siemens, Germany) and a radiation meter equipped with an ionization chamber. Results: The results consist of 153 iso-dose maps, which show the spatial distribution of DAP-normalized scattered air-kerma doses at the waist level of a pregnant worker. Conceptus dose estimation is possible using air-kerma to embryo/fetal dose conversion coefficients published in a previous study (J Cardiovasc Electrophysiol, Vol. 16, pp. 1–8, July 2005). Using these maps, occupationally exposed pregnant personnel may select a working position for a certain projection that keeps abdominal dose as low as reasonably achievable. Taking into consideration the regulatory conceptus dose limit for occupational exposure, determination of the maximum workload allowed for the pregnant personnel is also possible. Conclusion: Data produced in this work allow for the anticipation of conceptus dose and the determination of the maximum workload for a pregnant worker from any fluoroscopically-guided interventional procedure. This study was supported by the Greek Ministry of Education and Religious Affairs, General Secretariat for Research and Technology, Operational Program ‘Education and Lifelong Learning’, ARISTIA (Research project: CONCERT)« less

Radiation exposure of the radiologist's eye lens during CT-guided interventions.

PubMed

Heusch, Philipp; Kröpil, Patric; Buchbender, Christian; Aissa, Joel; Lanzman, Rotem S; Heusner, Till A; Ewen, Klaus; Antoch, Gerald; Fürst, Günther

2014-02-01

In the past decade the number of computed tomography (CT)-guided procedures performed by interventional radiologists have increased, leading to a significantly higher radiation exposure of the interventionalist's eye lens. Because of growing concern that there is a stochastic effect for the development of lens opacification, eye lens dose reduction for operators and patients should be of maximal interest. To determine the interventionalist's equivalent eye lens dose during CT-guided interventions and to relate the results to the maximum of the recommended equivalent dose limit. During 89 CT-guided interventions (e.g. biopsies, drainage procedures, etc.) measurements of eye lens' radiation doses were obtained from a dedicated dosimeter system for scattered radiation. The sensor of the personal dosimeter system was clipped onto the side of the lead glasses which was located nearest to the CT gantry. After the procedure, radiation dose (µSv), dose rate (µSv/min) and the total exposure time (s) were recorded. For all 89 interventions, the median total exposure lens dose was 3.3 µSv (range, 0.03-218.9 µSv) for a median exposure time of 26.2 s (range, 1.1-94.0 s). The median dose rate was 13.9 µSv/min (range, 1.1-335.5 µSv/min). Estimating 50-200 CT-guided interventions per year performed by one interventionalist, the median dose of the eye lens of the interventional radiologist does not exceed the maximum of the ICRP-recommended equivalent eye lens dose limit of 20 mSv per year.

Detailed Distribution Map of Absorbed Dose Rate in Air in Tokatsu Area of Chiba Prefecture, Japan, Constructed by Car-Borne Survey 4 Years after the Fukushima Daiichi Nuclear Power Plant Accident.

PubMed

Inoue, Kazumasa; Arai, Moeko; Fujisawa, Makoto; Saito, Kyouko; Fukushi, Masahiro

2017-01-01

A car-borne survey was carried out in the northwestern, or Tokatsu, area of Chiba Prefecture, Japan, to make a detailed distribution map of absorbed dose rate in air four years after the Fukushima Daiichi Nuclear Power Plant accident. This area was chosen because it was the most heavily radionuclide contaminated part of Chiba Prefecture and it neighbors metropolitan Tokyo. Measurements were performed using a 3-in × 3-in NaI(Tl) scintillation spectrometer in June 2015. The survey route covered the whole Tokatsu area which includes six cities. A heterogeneous distribution of absorbed dose rate in air was observed on the dose distribution map. Especially, higher absorbed dose rates in air exceeding 80 nGy h-1 were observed along national roads constructed using high porosity asphalt, whereas lower absorbed dose rates in air were observed along local roads constructed using low porosity asphalt. The difference between these asphalt types resulted in a heterogeneous dose distribution in the Tokatsu area. The mean of the contribution ratio of artificial radionuclides to absorbed dose rate in air measured 4 years after the accident was 29% (9-50%) in the Tokatsu area. The maximum absorbed dose rate in air, 201 nGy h-1 was observed at Kashiwa City. Radiocesium was deposited in the upper 1 cm surface layer of the high porosity asphalt which was collected in Kashiwa City and the environmental half-life of the absorbed dose rate in air was estimated to be 1.7 years.

Soft-tissue allografts terminally sterilized with an electron beam are biomechanically equivalent to aseptic, nonsterilized tendons.

PubMed

Elenes, Egleide Y; Hunter, Shawn A

2014-08-20

Allograft safety is contingent on effective sterilization. However, current sterilization methods have been associated with decreased biomechanical strength and higher failure rates of soft-tissue allografts. In this study, electron beam (e-beam) sterilization was explored as an alternative sterilization method to preserve biomechanical integrity. We hypothesized that e-beam sterilization would not significantly alter the biomechanical properties of tendon allograft compared with aseptic, nonsterilized controls and gamma-irradiated grafts. Separate sets of forty fresh-frozen tibialis tendon allografts (four from each of ten donors) and forty bisected bone-patellar tendon-bone (BTB) allografts (four from each of ten donors) were randomly assigned to four study groups. One group received a 17.1 to 21.0-kGy gamma radiation dose; two other groups were sterilized with an e-beam at either a high (17.1 to 21.0-kGy) or low (9.2 to 12.2-kGy) dose. A fourth group served as nonsterilized controls. Each graft was cyclically loaded to 200 N of tension for 2000 cycles at a frequency of 2 Hz, allowed to relax for five minutes, and then tested in tension until failure at a 100%/sec strain rate. One-way analysis of variance testing was used to identify significant differences. Tibialis tendons sterilized with both e-beam treatments and with gamma irradiation exhibited values for cyclic tendon elongation, maximum load, maximum displacement, stiffness, maximum stress, maximum strain, and elastic modulus that were not significantly different from those of nonsterilized controls. BTB allografts sterilized with the high e-beam dose and with gamma irradiation were not significantly different in cyclic tendon elongation, maximum load, maximum displacement, stiffness, maximum stress, maximum strain, and elastic modulus from nonsterilized controls. BTB allografts sterilized with the e-beam at the lower dose were significantly less stiff than nonsterilized controls (p = 0.014) but did not differ from controls in any other properties. The difference in stiffness likely resulted from variations in tendon size rather than the treatments, as the elastic moduli of the groups were similar. The biomechanical properties of tibialis and BTB allografts sterilized with use of an e-beam at a dose range of 17.1 to 21.0 kGy were not different from those of aseptic, nonsterilized controls or gamma-irradiated allografts. E-beam sterilization can be a viable method to produce safe and biomechanically uncompromised soft-tissue allografts. Copyright © 2014 by The Journal of Bone and Joint Surgery, Incorporated.

Effect of combined heat and radiation on microbial destruction

NASA Technical Reports Server (NTRS)

Fisher, D. A.; Pflug, I. J.

1977-01-01

A series of experiments at several levels of relative humidity and radiation dose rates was carried out using spores of Bacillus subtilis var. niger to evaluate the effect of heat alone, radiation alone, and a combination of heat and radiation. Combined heat and radiation treatment of microorganisms yields a destruction rate greater than the additive rates of the independent agents. The synergistic mechanism shows a proportional dependency on radiation dose rate, an Arrhenius dependence on temperature, and a dependency on relative humidity. Maximum synergism occurs under conditions where heat and radiation individually destroy microorganisms at approximately equal rates. Larger synergistic advantage is possible at low relative humidities rather than at high relative humidities.

The methodology study of time accelerated irradiation of elastomers

NASA Astrophysics Data System (ADS)

Ito, Masayuki

2005-07-01

The article studied the methods how to shorten the irradiation time by increasing dose rate without changing the relationship between dose versus properties of degraded samples. The samples used were nine kinds of EPDM which have different compounding formula. The different dose of Co-γ ray was exposed to the samples. The maximum dose was 2 MGy. The reference condition to be compared with two short time test conditions is irradiation of 0.33 kGy/h at room temperature. Two methods shown below were studied as the time-accelerate irradiation conditions.

Comparison of dose volume parameters evaluated using three forward planning – optimization techniques in cervical cancer brachytherapy involving two applicators

PubMed Central

Basu-Roy, Somapriya; Kar, Sanjay Kumar; Das, Sounik; Lahiri, Annesha

2017-01-01

Purpose This study is intended to compare dose-volume parameters evaluated using different forward planning- optimization techniques, involving two applicator systems in intracavitary brachytherapy for cervical cancer. It looks for the best applicator-optimization combination to fulfill recommended dose-volume objectives in different high-dose-rate (HDR) fractionation schedules. Material and methods We used tandem-ring and Fletcher-style tandem-ovoid applicator in same patients in two fractions of brachytherapy. Six plans were generated for each patient utilizing 3 forward optimization techniques for each applicator used: equal dwell weight/times (‘no optimization’), ‘manual dwell weight/times’, and ‘graphical’. Plans were normalized to left point A and dose of 8 Gy was prescribed. Dose volume and dose point parameters were compared. Results Without graphical optimization, maximum width and thickness of volume enclosed by 100% isodose line, dose to 90%, and 100% of clinical target volume (CTV); minimum, maximum, median, and average dose to both rectum and bladder are significantly higher with Fletcher applicator. Even if it is done, dose to both points B, minimum dose to CTV, and treatment time; dose to 2 cc (D2cc) rectum and rectal point etc.; D2cc, minimum, maximum, median, and average dose to sigmoid colon; D2cc of bladder remain significantly higher with this applicator. Dose to bladder point is similar (p > 0.05) between two applicators, after all optimization techniques. Conclusions Fletcher applicator generates higher dose to both CTV and organs at risk (2 cc volumes) after all optimization techniques. Dose restriction to rectum is possible using graphical optimization only during selected HDR fractionation schedules. Bladder always receives dose higher than recommended, and 2 cc sigmoid colon always gets permissible dose. Contrarily, graphical optimization with ring applicators fulfills all dose volume objectives in all HDR fractionations practiced. PMID:29204164

Detailed Distribution Map of Absorbed Dose Rate in Air in Tokatsu Area of Chiba Prefecture, Japan, Constructed by Car-Borne Survey 4 Years after the Fukushima Daiichi Nuclear Power Plant Accident

PubMed Central

Inoue, Kazumasa; Arai, Moeko; Fujisawa, Makoto; Saito, Kyouko; Fukushi, Masahiro

2017-01-01

A car-borne survey was carried out in the northwestern, or Tokatsu, area of Chiba Prefecture, Japan, to make a detailed distribution map of absorbed dose rate in air four years after the Fukushima Daiichi Nuclear Power Plant accident. This area was chosen because it was the most heavily radionuclide contaminated part of Chiba Prefecture and it neighbors metropolitan Tokyo. Measurements were performed using a 3-in × 3-in NaI(Tl) scintillation spectrometer in June 2015. The survey route covered the whole Tokatsu area which includes six cities. A heterogeneous distribution of absorbed dose rate in air was observed on the dose distribution map. Especially, higher absorbed dose rates in air exceeding 80 nGy h-1 were observed along national roads constructed using high porosity asphalt, whereas lower absorbed dose rates in air were observed along local roads constructed using low porosity asphalt. The difference between these asphalt types resulted in a heterogeneous dose distribution in the Tokatsu area. The mean of the contribution ratio of artificial radionuclides to absorbed dose rate in air measured 4 years after the accident was 29% (9–50%) in the Tokatsu area. The maximum absorbed dose rate in air, 201 nGy h-1 was observed at Kashiwa City. Radiocesium was deposited in the upper 1 cm surface layer of the high porosity asphalt which was collected in Kashiwa City and the environmental half-life of the absorbed dose rate in air was estimated to be 1.7 years. PMID:28129382

Stereotactic body radiation therapy of early-stage non-small-cell lung carcinoma: Phase I study

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGarry, Ronald C.; Papiez, Lech; Williams, Mark

Purpose: A Phase I dose escalation study of stereotactic body radiation therapy to assess toxicity and local control rates for patients with medically inoperable Stage I lung cancer. Methods and Materials: All patients had non-small-cell lung carcinoma, Stage T1a or T1b N0, M0. Patients were immobilized in a stereotactic body frame and treated in escalating doses of radiotherapy beginning at 24 Gy total (3 x 8 Gy fractions) using 7-10 beams. Cohorts were dose escalated by 6.0 Gy total with appropriate observation periods. Results: The maximum tolerated dose was not achieved in the T1 stratum (maximum dose = 60 Gy),more » but within the T2 stratum, the maximum tolerated dose was realized at 72 Gy for tumors larger than 5 cm. Dose-limiting toxicity included predominantly bronchitis, pericardial effusion, hypoxia, and pneumonitis. Local failure occurred in 4/19 T1 and 6/28 T2 patients. Nine local failures occurred at doses {<=}16 Gy and only 1 at higher doses. Local failures occurred between 3 and 31 months from treatment. Within the T1 group, 5 patients had distant or regional recurrence as an isolated event, whereas 3 patients had both distant and regional recurrence. Within the T2 group, 2 patients had solitary regional recurrences, and the 4 patients who failed distantly also failed regionally. Conclusions: Stereotactic body radiation therapy seems to be a safe, effective means of treating early-stage lung cancer in medically inoperable patients. Excellent local control was achieved at higher dose cohorts with apparent dose-limiting toxicities in patients with larger tumors.« less

SU-E-T-169: Characterization of Pacemaker/ICD Dose in SAVI HDR Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kalavagunta, C; Lasio, G; Yi, B

2015-06-15

Purpose: It is important to estimate dose to pacemaker (PM)/Implantable Cardioverter Defibrillator (ICD) before undertaking Accelerated Partial Breast Treatment using High Dose Rate (HDR) brachytherapy. Kim et al. have reported HDR PM/ICD dose using a single-source balloon applicator. To the authors knowledge, there have so far not been any published PM/ICD dosimetry literature for the Strut Adjusted Volume Implant (SAVI, Cianna Medical, Aliso Viejo, CA). This study aims to fill this gap by generating a dose look up table (LUT) to predict maximum dose to the PM/ICD in SAVI HDR brachytherapy. Methods: CT scans for 3D dosimetric planning were acquiredmore » for four SAVI applicators (6−1-mini, 6−1, 8−1 and 10−1) expanded to their maximum diameter in air. The CT datasets were imported into the Elekta Oncentra TPS for planning and each applicator was digitized in a multiplanar reconstruction window. A dose of 340 cGy was prescribed to the surface of a 1 cm expansion of the SAVI applicator cavity. Cartesian coordinates of the digitized applicator were determined in the treatment leading to the generation of a dose distribution and corresponding distance-dose prediction look up table (LUT) for distances from 2 to 15 cm (6-mini) and 2 to 20 cm (10–1).The deviation between the LUT doses and the dose to the cardiac device in a clinical case was evaluated. Results: Distance-dose look up table were compared to clinical SAVI plan and the discrepancy between the max dose predicted by the LUT and the clinical plan was found to be in the range (−0.44%, 0.74%) of the prescription dose. Conclusion: The distance-dose look up tables for SAVI applicators can be used to estimate the maximum dose to the ICD/PM, with a potential usefulness for quick assessment of dose to the cardiac device prior to applicator placement.« less

NOVEL HERBICIDES

EPA Science Inventory

Low-dose, high-potency herbicides are defined as those herbicides with a maximum label application rate of 0.5 pounds of active ingredient per acre. Several classes of chemicals fall into this category, including the acetolactate synthase (ALSase) inhibitor herbicides, imidazoli...

Terrestrial gamma radiation dose (TGRD) levels in northern zone of Jos Plateau, Nigeria: Statistical relationship between dose rates and geological formations

NASA Astrophysics Data System (ADS)

Abba, Habu Tela; Hassan, Wan Muhamad Saridan Wan; Saleh, Muneer Aziz; Aliyu, Abubakar Sadiq; Ramli, Ahmad Termizi

2017-11-01

In- situ measurement of terrestrial gamma radiation dose rates (TGRD) was conducted in northern zone of Jos Plateau and a statistical relationship between the TGRD and the underlying geological formations was investigated. The TGRD rates in all the measurements ranged from 40 to 1265 nGy h-1 with a mean value of 250 nGy h-1. The maximum TGDR was recorded on geological type G8 (Younger Granites) at Bisitchi, and the lowest TGDR was recorded on G6 (Basaltic rocks) at Gabia. One way analysis of variance (ANOVA) statistical test was used to compared the data. Significantly, the results of this study inferred a strong relationship between TGRD levels with geological structures of a place. An isodose map was plotted to represent exposure rates due to TGRD. The results of this investigation could be useful for multiple public interest such as evaluating public dose for the area.

Impact of cardiosynchronous brain pulsations on Monte Carlo calculated doses for synchrotron micro- and minibeam radiation therapy.

PubMed

Manchado de Sola, Francisco; Vilches, Manuel; Prezado, Yolanda; Lallena, Antonio M

2018-05-15

The purpose of this study was to assess the effects of brain movements induced by heartbeat on dose distributions in synchrotron micro- and minibeam radiation therapy and to develop a model to help guide decisions and planning for future clinical trials. The Monte Carlo code PENELOPE was used to simulate the irradiation of a human head phantom with a variety of micro- and minibeam arrays, with beams narrower than 100 μm and above 500 μm, respectively, and with radiation fields of 1 × 2 cm and 2 × 2 cm. The dose in the phantom due to these beams was calculated by superposing the dose profiles obtained for a single beam of 1 μm × 2 cm. A parameter δ, accounting for the total displacement of the brain during the irradiation and due to the cardiosynchronous pulsation, was used to quantify the impact on peak-to-valley dose ratios and the full width at half maximum. The difference between the maximum (at the phantom entrance) and the minimum (at the phantom exit) values of the peak-to-valley dose ratio reduces when the parameter δ increases. The full width at half maximum remains almost constant with depth for any δ value. Sudden changes in the two quantities are observed at the interfaces between the various tissues (brain, skull, and skin) present in the head phantom. The peak-to-valley dose ratio at the center of the head phantom reduces when δ increases, remaining above 70% of the static value only for minibeams and δ smaller than ∼200 μm. Optimal setups for brain treatments with synchrotron radiation micro- and minibeam combs depend on the brain displacement due to cardiosynchronous pulsation. Peak-to-valley dose ratios larger than 90% of the maximum values obtained in the static case occur only for minibeams and relatively large dose rates. © 2018 American Association of Physicists in Medicine.

[Value of early application of different doses of amino acids in parenteral nutrition among preterm infants].

PubMed

Liu, Zhi-Juan; Liu, Guo-Sheng; Chen, Yong-Ge; Zhang, Hui-Li; Wu, Xue-Fen

2015-01-01

To study the short-term response and tolerance of different doses of amino acids in parenteral nutrition among preterm infants. This study included 86 preterm infants who had a birth weight between 1 000 to 2 000 g and were admitted to the hospital within 24 hours of birth between March 2013 and June 2014. According to the early application of different doses of amino acids, they were randomized into low-dose group (n=29, 1.0 g/kg per day with an increase of 1.0 g/kg daily and a maximum of 3.5 g/kg per day), medium-dose group (n=28, 2.0 g/kg per day with an increase of 1.0 g/kg daily and a maximum of 3.7 g/kg per day), and high-dose group (n=29, 3.0 g/kg per day with an increase of 0.5-1.0 g/kg daily and a maximum of 4.0 g/kg per day). Other routine parenteral nutrition and enteral nutrition support were also applied. The maximum weight loss was lower and the growth rate of head circumference was greater in the high-dose group than in the low-dose group (P<0.05). The infants in the medium- and high-dose groups had faster recovery of birth weight, earlier attainment of 100 kcal/(kg·d) of enteral nutrition, shorter duration of hospital stay, and less hospital cost than those in the low-dose group (P<0.05). Blood urea nitrogen (BUN) levels in the high-dose group increased compared with the other two groups 7 days after birth (P<0.05). The levels of creatinine, pH, bicarbonate, bilirubin, and transaminase and the incidence of complications showed no significant differences between groups (P>0.05). Parenteral administration of high-dose amino acids in preterm infants within 24 hours after birth can improve the short-term nutritional status of preterm infants, but there is a transient increase in BUN level.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Laurinat, J.; Kesterson, M.; Hensel, S.

The documented safety analysis for the Savannah River Site evaluates the consequences of a postulated 1000 °C fire in a glovebox. The radiological dose consequences for a pressurized release of plutonium oxide powder during such a fire depend on the maximum pressure that is attained inside the oxide storage vial. To enable evaluation of the dose consequences, pressure transients and venting flow rates have been calculated for exposure of the storage vial to the fire. A standard B vial with a capacity of approximately 8 cc was selected for analysis. The analysis compares the pressurization rate from heating and evaporationmore » of moisture adsorbed onto the plutonium oxide contents of the vial with the pressure loss due to venting of gas through the threaded connection between the vial cap and body. Tabulated results from the analysis include maximum pressures, maximum venting velocities, and cumulative vial volumes vented during the first 10 minutes of the fire transient. Results are obtained for various amounts of oxide in the vial, various amounts of adsorbed moisture, different vial orientations, and different surface fire exposures.« less

Factors Associated With Chest Wall Toxicity After Accelerated Partial Breast Irradiation Using High-Dose-Rate Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, Sheree, E-mail: shereedst32@hotmail.com; Vicini, Frank; Vanapalli, Jyotsna R.

2012-07-01

Purpose: The purpose of this analysis was to evaluate dose-volume relationships associated with a higher probability for developing chest wall toxicity (pain) after accelerated partial breast irradiation (APBI) by using both single-lumen and multilumen brachytherapy. Methods and Materials: Rib dose data were available for 89 patients treated with APBI and were correlated with the development of chest wall/rib pain at any point after treatment. Ribs were contoured on computed tomography planning scans, and rib dose-volume histograms (DVH) along with histograms for other structures were constructed. Rib DVH data for all patients were sampled at all volumes {>=}0.008 cubic centimeter (cc)more » (for maximum dose related to pain) and at volumes of 0.5, 1, 2, and 3 cc for analysis. Rib pain was evaluated at each follow-up visit. Patient responses were marked as yes or no. No attempt was made to grade responses. Eighty-nine responses were available for this analysis. Results: Nineteen patients (21.3%) complained of transient chest wall/rib pain at any point in follow-up. Analysis showed a direct correlation between total dose received and volume of rib irradiated with the probability of developing rib/chest wall pain at any point after follow-up. The median maximum dose at volumes {>=}0.008 cc of rib in patients who experienced chest wall pain was 132% of the prescribed dose versus 95% of the prescribed dose in those patients who did not experience pain (p = 0.0035). Conclusions: Although the incidence of chest wall/rib pain is quite low with APBI brachytherapy, attempts should be made to keep the volume of rib irradiated at a minimum and the maximum dose received by the chest wall as low as reasonably achievable.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, X

Purpose: To explore the real-time dose verification method in volumetric modulated arc radiotherapy (VMAT) with a 2D array ion chamber array. Methods: The 2D ion chamber array was fixed on the panel of electronic portal imaging device (EPID). Source-detector distance (SDD)was 140cm. 8mm RW3 solid water was added to the detector panel to achieve maximum readings.The patient plans for esophageal, prostate and liver cancers were selected to deliver on the cylindrical Cheese phantom 5 times in order to validate the reproducibility of doses. Real-time patient transit dose measurements were performed at each fraction. Dose distributions wereevaluated using gamma index criteriamore » of 3mm DTA and 3% dose difference referred to the firsttime Result. Results: The gamma index pass rate in the Cheese phantom were about 98%; The gamma index pass rate for esophageal, liver and prostate cancer patient were about 92%,94%, and 92%, respectively; Gamma pass rate for all single fraction were more than 90%. Conclusion: The 2D array is capable of monitoring the real time transit doses during VMAT delivery. It is helpful to improve the treatment accuracy.« less

Effect of ozonation on the reactivity of lignocellulose substrates in enzymatic hydrolyses to sugars

NASA Astrophysics Data System (ADS)

Ben'ko, E. M.; Manisova, O. R.; Lunin, V. V.

2013-07-01

The efficiency of pre-treatment of aspen wood with ozone for subsequent enzymatic hydrolysis into sugars is determined by the amount of absorbed ozone. The ozone absorption rate depended on the water content in the sample being ozonized and was maximum at a relative humidity of wood of ˜40%. As a result of ozone pre-treatment, the initial rate of the enzymatic hydrolysis of wood under the action of a cellulase complex increased eightfold, and the maximum yield of sugars increased tenfold depending on the ozone dose. The ozonation at ozone doses of more than 3 mol/PPU (phenylpropane structural unit of lignin) led to a decrease in the yield of sugars because of the oxidative destruction of cellulose and hemicellulose. The alkaline ozonation in 2 and 12% NaOH was inefficient because of the accompanying oxidation of carbohydrates and considerably decreased the yield of sugars.

Estimation of dose rates at the entrance surface for exposure scenarios of total body irradiation using MCNPX code

NASA Astrophysics Data System (ADS)

Cunha, J. S.; Cavalcante, F. R.; Souza, S. O.; Souza, D. N.; Santos, W. S.; Carvalho Júnior, A. B.

2017-11-01

One of the main criteria that must be held in Total Body Irradiation (TBI) is the uniformity of dose in the body. In TBI procedures the certification that the prescribed doses are absorbed in organs is made with dosimeters positioned on the patient skin. In this work, we modelled TBI scenarios in the MCNPX code to estimate the entrance dose rate in the skin for comparison and validation of simulations with experimental measurements from literature. Dose rates were estimated simulating an ionization chamber laterally positioned on thorax, abdomen, leg and thigh. Four exposure scenarios were simulated: ionization chamber (S1), TBI room (S2), and patient represented by hybrid phantom (S3) and water stylized phantom (S4) in sitting posture. The posture of the patient in experimental work was better represented by S4 compared with hybrid phantom, and this led to minimum and maximum percentage differences of 1.31% and 6.25% to experimental measurements for thorax and thigh regions, respectively. As for all simulations reported here the percentage differences in the estimated dose rates were less than 10%, we considered that the obtained results are consistent with experimental measurements and the modelled scenarios are suitable to estimate the absorbed dose in organs during TBI procedure.

[Methodology for an assessment of derived radiation levels for agrocenoses].

PubMed

Udalova, A A; Ul'ianenko, L N; Aleksakhin, R M; Geras'kin, S A; Filipas, A S

2010-01-01

Radiation protection of agrarian ecosystems should be considered as an integral part of a system for radiation protection of environment, with a special concern to agroecosystems' features. A methodology is proposed for an assessment of maximum permissible doses of radiation impact for agrocenoses based on an unified analysis of available data about effects of radiation in cultivated plants. It is considered as a component of radiation protection system for agricultural ecosystems. Critical doses and dose rates are estimated for crops under different exposure situations. It is shown that doses that could result in decreasing indexes of productivity and survival for main crops below 50% are unlikely up to 170-200 Gy and 15-17 Gy at an acute exposure of dormant seeds and vegetative plants, correspondingly. At chronic exposure, above 10% loss of productivity in crops is not expected at dose rates below 3-10 mGy/h.

An open-label, dose-titration tolerability study of atomoxetine hydrochloride in Japanese adults with attention-deficit/hyperactivity disorder.

PubMed

Takahashi, Michihiro; Takita, Yasushi; Goto, Taro; Ichikawa, Hironobu; Saito, Kazuhiko; Matsumoto, Hideo; Tanaka, Yasuo

2011-02-01

The main purpose of this first atomoxetine study in Japanese adults with attention-deficit/hyperactivity disorder (ADHD) was to investigate the tolerability of an 8-week treatment regimen. This was an open-label, dose escalation study conducted in 45 Japanese patients aged at least 18 years with DSM-IV-defined ADHD. Patients received atomoxetine orally for 8 weeks. Atomoxetine administration was started at 40 mg/day (7 days), and subsequently increased to a maximum dose of 120 mg/day. Tolerability was assessed by discontinuation rate due to adverse events. Adverse events, laboratory tests, vital signs and electrocardiograms were collected. In addition, ADHD symptoms were assessed by using the Japanese version of the Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) scores. Thirty-nine patients completed the study period. Atomoxetine was well tolerated with a 6.7% (3/45) discontinuation rate due to nausea, malaise and anorexia. The most commonly reported adverse events were nausea, nasopharyngitis and headache; there were no unexpected safety concerns. No deaths or serious adverse events were reported. Mean CAARS-Inv:SV-J total ADHD symptom scores decreased in a time-dependent manner; the mean change from baseline to endpoint was -15.0 (P<0.001). This study showed that atomoxetine was well tolerated in these patients and suggested that atomoxetine at a maximum dose of 120 mg/day would be safe in Japanese ADHD patients. © 2011 The Authors. Psychiatry and Clinical Neurosciences © 2011 Japanese Society of Psychiatry and Neurology.

Erlotinib in African Americans with Advanced Non-Small Cell Lung Cancer: A Prospective Randomized Study with Genetic and Pharmacokinetic Analysis

PubMed Central

Phelps, Mitch A.; Stinchcombe, Thomas E.; Blachly, James S.; Zhao, Weiqiang; Schaaf, Larry J.; Starrett, Sherri L.; Wei, Lai; Poi, Ming; Wang, Danxin; Papp, Audrey; Aimiuwu, Josephine; Gao, Yue; Li, Junan; Otterson, Gregory A.; Hicks, William J.; Socinski, Mark A.; Villalona-Calero, Miguel A.

2014-01-01

Prospective studies focusing on EGFR inhibitors in African Americans with NSCLC have not been previously performed. In this phase II randomized study, 55 African Americans with NSCLC received erlotinib 150mg/day or a body weight adjusted dose with subsequent escalations to the maximum allowable, 200mg/day, to achieve rash. Erlotinib and OSI-420 exposures were lower compared to previous reports, consistent with CYP3A pharmacogenetics implying higher metabolic activity. Tumor genetics revealed only two EGFR mutations, EGFR amplification in 17/47 samples, 8 KRAS mutations and 5 EML4-ALK translocations. Although absence of rash was associated with shorter time to progression (TTP), disease control rate, TTP, and 1-year survival were not different between the two dose groups, indicating the dose-to-rash strategy failed to increase clinical benefit. Observed low incidence of toxicity and low erlotinib exposure suggest standardized and maximum allowable dosing may be suboptimal in African Americans. PMID:24781527

High resolution digital autoradiographic and dosimetric analysis of heterogeneous radioactivity distribution in xenografted prostate tumors.

PubMed

Timmermand, Oskar V; Nilsson, Jenny; Strand, Sven-Erik; Elgqvist, Jörgen

2016-12-01

The first main aim of this study was to illustrate the absorbed dose rate distribution from 177 Lu in sections of xenografted prostate cancer (PCa) tumors using high resolution digital autoradiography (DAR) and compare it with hypothetical identical radioactivity distributions of 90 Y or 7 MeV alpha-particles. Three dosimetry models based on either dose point kernels or Monte Carlo simulations were used and evaluated. The second and overlapping aim, was to perform DAR imaging and dosimetric analysis of the distribution of radioactivity, and hence the absorbed dose rate, in tumor sections at an early time point after injection during radioimmunotherapy using 177 Lu-h11B6, directed against the human kallikrein 2 antigen. Male immunodeficient BALB/c nude mice, aged 6-8 w, were inoculated by subcutaneous injection of ∼10 7 LNCaP cells in a 200 μl suspension of a 1:1 mixture of medium and Matrigel. The antibody h11B6 was conjugated with the chelator CHX-A″-DTPA after which conjugated h11B6 was mixed with 177 LuCl 3 . The incubation was performed at room temperature for 2 h, after which the labeling was terminated and the solution was purified on a NAP-5 column. About 20 MBq 177 Lu-h11B6 was injected intravenously in the tail vein. At approximately 10 h postinjection (hpi), the mice were sacrificed and one tumor was collected from each of the five animals and cryosectioned into 10 μm thick slices. The tumor slices were measured and imaged using the DAR MicroImager system and the M3Vision software. Then the absorbed dose rate was calculated using a dose point kernel generated with the Monte Carlo code gate v7.0. The DAR system produced high resolution images of the radioactivity distribution, close to the resolution of single PCa cells. The DAR images revealed a pronounced heterogeneous radioactivity distribution, i.e., count rate per area, in the tumors, indicated by the normalized intensity variations along cross sections as mean ± SD: 0.15 ± 0.15, 0.20 ± 0.18, 0.12 ± 0.17, 0.15 ± 0.16, and 0.23 ± 0.22, for each tumor section, respectively. The absorbed dose rate distribution for 177 Lu at the time of dissection 10 hpi showed a maximum value of 2.9 ± 0.4 Gy/h (mean ± SD), compared to 6.0 ± 0.9 and 159 ± 25 Gy/h for the hypothetical 90 Y and 7 MeV alpha-particle cases assuming the same count rate densities. Mean absorbed dose rate values were 0.13, 0.53, and 6.43 Gy/h for 177 Lu, 90 Y, and alpha-particles, respectively. The initial uptake of 177 Lu-h11B6 produces a high absorbed dose rate, which is important for a successful therapeutic outcome. The hypothetical 90 Y case indicates a less heterogeneous absorbed dose rate distribution and a higher mean absorbed dose rate compared to 177 Lu, although with a potentially increased irradiation of surrounding healthy tissue. The hypothetical alpha-particle case indicates the possibility of a higher maximum absorbed dose rate, although with a more heterogeneous absorbed dose rate distribution.

Identifying the most successful dose (MSD) in dose-finding studies in cancer.

PubMed

Zohar, Sarah; O'Quigley, John

2006-01-01

For a dose finding study in cancer, the most successful dose (MSD), among a group of available doses, is that dose at which the overall success rate is the highest. This rate is the product of the rate of seeing non-toxicities together with the rate of tumor response. A successful dose finding trial in this context is one where we manage to identify the MSD in an efficient manner. In practice we may also need to consider algorithms for identifying the MSD which can incorporate certain restrictions, the most common restriction maintaining the estimated toxicity rate alone below some maximum rate. In this case the MSD may correspond to a different level than that for the unconstrained MSD and, in providing a final recommendation, it is important to underline that it is subject to the given constraint. We work with the approach described in O'Quigley et al. [Biometrics 2001; 57(4):1018-1029]. The focus of that work was dose finding in HIV where both information on toxicity and efficacy were almost immediately available. Recent cancer studies are beginning to fall under this same heading where, as before, toxicity can be quickly evaluated and, in addition, we can rely on biological markers or other measures of tumor response. Mindful of the particular context of cancer, our purpose here is to consider the methodology developed by O'Quigley et al. and its practical implementation. We also carry out a study on the doubly under-parameterized model, developed by O'Quigley et al. but not

Nitric oxide evokes pain in humans on intracutaneous injection.

PubMed

Holthusen, H; Arndt, J O

1994-01-03

To test the hypothesis that nitric oxide (NO) acts algetically in humans, we determined pain intensity/dose relations for intracutaneously applied NO solutions. NO, dissolved in isoosmolar phosphate buffer, was injected in the forearm of six volunteers and the subjects rated NO-evoked pain continuously with the help of an electronically controlled visual analogue scale. Pain always occurred at a NO dose of 12 nmol, increased with dose and reached the tolerance maximum at 50 nmol. This shows for the first time the genuine pain evoking properties of NO.

Lifetimes and spatio-temporal response of protein crystals in intense X-ray microbeams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Warkentin, Matthew A.; Atakisi, Hakan; Hopkins, Jesse B.

Serial synchrotron-based crystallography using intense microfocused X-ray beams, fast-framing detectors and protein microcrystals held at 300 K promises to expand the range of accessible structural targets and to increase overall structure-pipeline throughputs. To explore the nature and consequences of X-ray radiation damage under microbeam illumination, the time-, dose- and temperature-dependent evolution of crystal diffraction have been measured with maximum dose rates of 50 MGy s −1 . At all temperatures and dose rates, the integrated diffraction intensity for a fixed crystal orientation shows non-exponential decays with dose. Non-exponential decays are a consequence of non-uniform illumination and the resulting spatial evolution of diffracted intensitymore » within the illuminated crystal volume. To quantify radiation-damage lifetimes and the damage state of diffracting crystal regions, a revised diffraction-weighted dose (DWD) is defined and it is shown that for Gaussian beams the DWD becomes nearly independent of actual dose at large doses. An apparent delayed onset of radiation damage seen in some intensity–dose curves is in fact a consequence of damage. Intensity fluctuations at high dose rates may arise from the impulsive release of gaseous damage products. Accounting for these effects, data collection at the highest dose rates increases crystal radiation lifetimes near 300 K (but not at 100 K) by a factor of ∼1.5–2 compared with those observed at conventional dose rates. Improved quantification and modeling of the complex spatio-temporal evolution of protein microcrystal diffraction in intense microbeams will enable more efficient data collection, and will be essential in improving the accuracy of structure factors and structural models.« less

Lifetimes and spatio-temporal response of protein crystals in intense X-ray microbeams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Warkentin, Matthew A.; Atakisi, Hakan; Hopkins, Jesse B.

Serial synchrotron-based crystallography using intense microfocused X-ray beams, fast-framing detectors and protein microcrystals held at 300 K promises to expand the range of accessible structural targets and to increase overall structure-pipeline throughputs. To explore the nature and consequences of X-ray radiation damage under microbeam illumination, the time-, dose- and temperature-dependent evolution of crystal diffraction have been measured with maximum dose rates of 50 MGy s –1. At all temperatures and dose rates, the integrated diffraction intensity for a fixed crystal orientation shows non-exponential decays with dose. Non-exponential decays are a consequence of non-uniform illumination and the resulting spatial evolution ofmore » diffracted intensity within the illuminated crystal volume. To quantify radiation-damage lifetimes and the damage state of diffracting crystal regions, a revised diffraction-weighted dose (DWD) is defined and it is shown that for Gaussian beams the DWD becomes nearly independent of actual dose at large doses. An apparent delayed onset of radiation damage seen in some intensity–dose curves is in fact a consequence of damage. Intensity fluctuations at high dose rates may arise from the impulsive release of gaseous damage products. Accounting for these effects, data collection at the highest dose rates increases crystal radiation lifetimes near 300 K (but not at 100 K) by a factor of ~1.5–2 compared with those observed at conventional dose rates. As a result, improved quantification and modeling of the complex spatio-temporal evolution of protein microcrystal diffraction in intense microbeams will enable more efficient data collection, and will be essential in improving the accuracy of structure factors and structural models.« less

Lifetimes and spatio-temporal response of protein crystals in intense X-ray microbeams

DOE PAGES

Warkentin, Matthew A.; Atakisi, Hakan; Hopkins, Jesse B.; ...

2017-10-13

Serial synchrotron-based crystallography using intense microfocused X-ray beams, fast-framing detectors and protein microcrystals held at 300 K promises to expand the range of accessible structural targets and to increase overall structure-pipeline throughputs. To explore the nature and consequences of X-ray radiation damage under microbeam illumination, the time-, dose- and temperature-dependent evolution of crystal diffraction have been measured with maximum dose rates of 50 MGy s –1. At all temperatures and dose rates, the integrated diffraction intensity for a fixed crystal orientation shows non-exponential decays with dose. Non-exponential decays are a consequence of non-uniform illumination and the resulting spatial evolution ofmore » diffracted intensity within the illuminated crystal volume. To quantify radiation-damage lifetimes and the damage state of diffracting crystal regions, a revised diffraction-weighted dose (DWD) is defined and it is shown that for Gaussian beams the DWD becomes nearly independent of actual dose at large doses. An apparent delayed onset of radiation damage seen in some intensity–dose curves is in fact a consequence of damage. Intensity fluctuations at high dose rates may arise from the impulsive release of gaseous damage products. Accounting for these effects, data collection at the highest dose rates increases crystal radiation lifetimes near 300 K (but not at 100 K) by a factor of ~1.5–2 compared with those observed at conventional dose rates. As a result, improved quantification and modeling of the complex spatio-temporal evolution of protein microcrystal diffraction in intense microbeams will enable more efficient data collection, and will be essential in improving the accuracy of structure factors and structural models.« less

Lifetimes and spatio-temporal response of protein crystals in intense X-ray microbeams

DOE PAGES

Warkentin, Matthew A.; Atakisi, Hakan; Hopkins, Jesse B.; ...

2017-10-13

Serial synchrotron-based crystallography using intense microfocused X-ray beams, fast-framing detectors and protein microcrystals held at 300 K promises to expand the range of accessible structural targets and to increase overall structure-pipeline throughputs. To explore the nature and consequences of X-ray radiation damage under microbeam illumination, the time-, dose- and temperature-dependent evolution of crystal diffraction have been measured with maximum dose rates of 50 MGy s −1 . At all temperatures and dose rates, the integrated diffraction intensity for a fixed crystal orientation shows non-exponential decays with dose. Non-exponential decays are a consequence of non-uniform illumination and the resulting spatial evolution of diffracted intensitymore » within the illuminated crystal volume. To quantify radiation-damage lifetimes and the damage state of diffracting crystal regions, a revised diffraction-weighted dose (DWD) is defined and it is shown that for Gaussian beams the DWD becomes nearly independent of actual dose at large doses. An apparent delayed onset of radiation damage seen in some intensity–dose curves is in fact a consequence of damage. Intensity fluctuations at high dose rates may arise from the impulsive release of gaseous damage products. Accounting for these effects, data collection at the highest dose rates increases crystal radiation lifetimes near 300 K (but not at 100 K) by a factor of ∼1.5–2 compared with those observed at conventional dose rates. Improved quantification and modeling of the complex spatio-temporal evolution of protein microcrystal diffraction in intense microbeams will enable more efficient data collection, and will be essential in improving the accuracy of structure factors and structural models.« less

SU-E-T-607: Performance Quantification of the Nine Detectors Used for Dosimetry Measurements in Advanced Radiation Therapy Treatments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Markovic, M; Stathakis, S; Jurkovic, I

2015-06-15

Purpose: The purpose of this study was to quantify performance of the nine detectors used for dosimetry measurements in advanced radiation therapy treatments. Methods: The 6 MV beam was utilized for measurements of the field sizes with the lack of lateral charge particle equilibrium. For dose fidelity aspect, energy dependence was studied by measuring PDD and profiles at different depths. The volume effect and its influence on the measured dose profiles have been observed by measuring detector’s response function. Output factor measurements with respect to change in energy spectrum have been performed and collected data has been analyzed. The linearitymore » of the measurements with the dose delivered has been evaluated and relevant comparisons were done. Results: The measured values of the output factors with respect to change in energy spectrum indicated presence of the energy dependence. The detectors with active volume size ≤ 0.3 mm3 maximum deviation from the mean is 5.6% for the field size 0.5 x 0.5 cm2 while detectors with active volume size > 0.3 mm3 have maximum deviation from the mean 7.1%. Linearity with dose at highest dose rate examined for diode detectors showed maximum deviation of 4% while ion chambers showed maximum deviation of 2.2%. Dose profiles showed energy dependence at shallow depths (surface to dmax) influenced by low energy particles with 12 % maximum deviation from the mean for 5 mm2 field size. In relation to Monte Carlo calculation, the detector’s response function σ values were between (0.42±0.25) mm and (1.2±0.25) mm. Conclusion: All the detectors are appropriate for the dosimetry measurements in advanced radiation therapy treatments. The choice of the detectors has to be determined by the application and the scope of the measurements in respect to energy dependence and ability to accurately resolve dose profiles as well as to it’s intrinsic characteristics.« less

Ionizing radiation induces O6-alkylguanine-DNA-alkyltransferase mRNA and activity in mouse tissues.

PubMed

Wilson, R E; Hoey, B; Margison, G P

1993-04-01

The effect of exposure to whole-body gamma-irradiation or fast electrons on O6-alkylguanine-DNA-alkyltransferase (ATase) activity and mRNA abundance has been examined in mice. In response to gamma-radiation, hepatic ATase activity was significantly raised in BDF1 mice 24 h post-irradiation, reaching a maximum of 2- to 3-fold at 36 h and beginning to decrease by 48-60 h. A small but consistently higher level of induction was achieved when mice were exposed using a low dose rate (0.015 Gy/min) compared to a high dose rate (0.5 Gy/min). ATase activity was also induced approximately 2-fold 48 h post-irradiation in brain, kidney, lung and spleen, with a greater induction again observed in response to the lower dose rate. In response to fast electrons from a linear accelerator hepatic ATase activity was also induced 2- to 3-fold 48 h post-irradiation in BDF1, BALB/c, C57Bl and DBA2 strains. Induction of ATase activity in livers of BDF1 mice was observed 48 h after a total single dose of 5 Gy gamma-radiation (2-fold), increasing to a slightly higher level at 15 Gy, but no induction was observed at doses of 2 Gy and below. Although a maximum 2- to 3-fold induction of ATase activity was observed, mRNA levels were induced 3- to 4-fold by 48 h after a dose of 15 Gy. Furthermore, significant increases in mRNA levels were detected at low doses (1-2 Gy) at which there was no apparent increase in ATase activity. This suggests that ionizing radiation increases ATase levels by a process involving transcriptional upregulation but that strong post-transcriptional and/or translational controls operate to limit induction of enzyme activity to 2- to 3-fold. This is the first report of an in vivo induction of ATase by ionizing radiation in a species other than the rat.

Early photosensitizer uptake kinetics predict optimum drug-light interval for photodynamic therapy

NASA Astrophysics Data System (ADS)

Sinha, Lagnojita; Elliott, Jonathan T.; Hasan, Tayyaba; Pogue, Brian W.; Samkoe, Kimberley S.; Tichauer, Kenneth M.

2015-03-01

Photodynamic therapy (PDT) has shown promising results in targeted treatment of cancerous cells by developing localized toxicity with the help of light induced generation of reactive molecular species. The efficiency of this therapy depends on the product of the intensity of light dose and the concentration of photosensitizer (PS) in the region of interest (ROI). On account of this, the dynamic and variable nature of PS delivery and retention depends on many physiological factors that are known to be heterogeneous within and amongst tumors (e.g., blood flow, blood volume, vascular permeability, and lymph drainage rate). This presents a major challenge with respect to how the optimal time and interval of light delivery is chosen, which ideally would be when the concentration of PS molecule is at its maximum in the ROI. In this paper, a predictive algorithm is developed that takes into consideration the variability and dynamic nature of PS distribution in the body on a region-by-region basis and provides an estimate of the optimum time when the PS concentration will be maximum in the ROI. The advantage of the algorithm lies in the fact that it predicts the time in advance as it takes only a sample of initial data points (~12 min) as input. The optimum time calculated using the algorithm estimated a maximum dose that was only 0.58 +/- 1.92% under the true maximum dose compared to a mean dose error of 39.85 +/- 6.45% if a 1 h optimal light deliver time was assumed for patients with different efflux rate constants of the PS, assuming they have the same plasma function. Therefore, if the uptake values of PS for the blood and the ROI is known for only first 12 minutes, the entire curve along with the optimum time of light radiation can be predicted with the help of this algorithm.

Dose Calculations for [131I] Meta-Iodobenzylguanidine-Induced Bystander Effects

PubMed Central

Gow, M. D.; Seymour, C. B.; Boyd, M.; Mairs, R. J.; Prestiwch, W. V.; Mothersill, C. E.

2014-01-01

Targeted radiotherapy is a potentially useful treatment for some cancers and may be potentiated by bystander effects. However, without estimation of absorbed dose, it is difficult to compare the effects with conventional external radiation treatment. Methods: Using the Vynckier – Wambersie dose point kernel, a model for dose rate evaluation was created allowing for calculation of absorbed dose values to two cell lines transfected with the noradrenaline transporter (NAT) gene and treated with [131I]MIBG. Results: The mean doses required to decrease surviving fractions of UVW/NAT and EJ138/NAT cells, which received medium from [131I]MIBG-treated cells, to 25 – 30% were 1.6 and 1.7 Gy respectively. The maximum mean dose rates achieved during [131I]MIBG treatment were 0.09 – 0.75 Gy/h for UVW/NAT and 0.07 – 0.78 Gy/h for EJ138/NAT. These were significantly lower than the external beam gamma radiation dose rate of 15 Gy/h. In the case of control lines which were incapable of [131I]MIBG uptake the mean absorbed doses following radiopharmaceutical were 0.03 – 0.23 Gy for UVW and 0.03 – 0.32 Gy for EJ138. Conclusion: [131I]MIBG treatment for ICCM production elicited a bystander dose-response profile similar to that generated by external beam gamma irradiation but with significantly greater cell death. PMID:24659931

Lithospheric flexure revealed by Pleistocene emerged marine terraces on the southern Hawaiian Islands

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jones, A.T.

1992-01-01

New field and geochronological data from emerged marine deposits in the southern Hawaiian Islands suggest uplift of the islands of Molokai, Lanai and Oahu. Corals from these islands were dated by ESR. The accumulated dose for aragonitic coral at ESR signal, g = 2.0007, was determined by the additive dose method. The environmental dose rate was estimated from the Uranium concentration in corals and by using an estimate of 2.5 rad/a for the cosmic ray dose. The ESR ages of the highest terraces on Molokai are 290 [+-] 31 ka (30 m), on Lanai 217 [+-] 19 ka (50 m)more » and on Oahu 468 [+-] 36 ka (28 m). The age and elevation of the marine terraces are interpreted to imply uplift during the Late Quaternary. Lithospheric flexure combined with horizontal plate motion is proposed as a mechanism to describe the pattern of uplifted terraces on these islands. Using two-dimensional elastic plate models, the height of maximum bulge is approximately 4% to 7% of the maximum deflection for a continuous or broken plate model. Drowned reefs off Hawaii indicate subsidence of 1 km since 340 ka. Thus, the magnitude of observed uplift (30--50 m) is consistent with theoretical maximum bulge heights derived from numerical results.« less

T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial.

PubMed

Lee, Daniel W; Kochenderfer, James N; Stetler-Stevenson, Maryalice; Cui, Yongzhi K; Delbrook, Cindy; Feldman, Steven A; Fry, Terry J; Orentas, Rimas; Sabatino, Marianna; Shah, Nirali N; Steinberg, Seth M; Stroncek, Dave; Tschernia, Nick; Yuan, Constance; Zhang, Hua; Zhang, Ling; Rosenberg, Steven A; Wayne, Alan S; Mackall, Crystal L

2015-02-07

Chimeric antigen receptor (CAR) modified T cells targeting CD19 have shown activity in case series of patients with acute and chronic lymphocytic leukaemia and B-cell lymphomas, but feasibility, toxicity, and response rates of consecutively enrolled patients treated with a consistent regimen and assessed on an intention-to-treat basis have not been reported. We aimed to define feasibility, toxicity, maximum tolerated dose, response rate, and biological correlates of response in children and young adults with refractory B-cell malignancies treated with CD19-CAR T cells. This phase 1, dose-escalation trial consecutively enrolled children and young adults (aged 1-30 years) with relapsed or refractory acute lymphoblastic leukaemia or non-Hodgkin lymphoma. Autologous T cells were engineered via an 11-day manufacturing process to express a CD19-CAR incorporating an anti-CD19 single-chain variable fragment plus TCR zeta and CD28 signalling domains. All patients received fludarabine and cyclophosphamide before a single infusion of CD19-CAR T cells. Using a standard 3 + 3 design to establish the maximum tolerated dose, patients received either 1 × 10(6) CAR-transduced T cells per kg (dose 1), 3 × 10(6) CAR-transduced T cells per kg (dose 2), or the entire CAR T-cell product if sufficient numbers of cells to meet the assigned dose were not generated. After the dose-escalation phase, an expansion cohort was treated at the maximum tolerated dose. The trial is registered with ClinicalTrials.gov, number NCT01593696. Between July 2, 2012, and June 20, 2014, 21 patients (including eight who had previously undergone allogeneic haematopoietic stem-cell transplantation) were enrolled and infused with CD19-CAR T cells. 19 received the prescribed dose of CD19-CAR T cells, whereas the assigned dose concentration could not be generated for two patients (90% feasible). All patients enrolled were assessed for response. The maximum tolerated dose was defined as 1 × 10(6) CD19-CAR T cells per kg. All toxicities were fully reversible, with the most severe being grade 4 cytokine release syndrome that occurred in three (14%) of 21 patients (95% CI 3·0-36·3). The most common non-haematological grade 3 adverse events were fever (nine [43%] of 21 patients), hypokalaemia (nine [43%] of 21 patients), fever and neutropenia (eight [38%] of 21 patients), and cytokine release syndrome (three [14%) of 21 patients). CD19-CAR T cell therapy is feasible, safe, and mediates potent anti-leukaemic activity in children and young adults with chemotherapy-resistant B-precursor acute lymphoblastic leukaemia. All toxicities were reversible and prolonged B-cell aplasia did not occur. National Institutes of Health Intramural funds and St Baldrick's Foundation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Interplay effect on a 6-MV flattening-filter-free linear accelerator with high dose rate and fast multi-leaf collimator motion treating breast and lung phantoms.

PubMed

Netherton, Tucker; Li, Yuting; Nitsch, Paige; Shaitelman, Simona; Balter, Peter; Gao, Song; Klopp, Ann; Muruganandham, Manickam; Court, Laurence

2018-06-01

Using a new linear accelerator with high dose rate (800 MU/min), fast MLC motions (5.0 cm/s), fast gantry rotation (15 s/rotation), and 1 cm wide MLCs, we aimed to quantify the effects of complexity, arc number, and fractionation on interplay for breast and lung treatments under target motion. To study lung interplay, eight VMAT plans (1-6 arcs) and four-nine-field sliding-window IMRT plans varying in complexity were created. For the breast plans, four-four-field sliding-window IMRT plans were created. Using the Halcyon 1.0 linear accelerator, each plan was delivered five times each under sinusoidal breathing motion to a phantom with 20 implanted MOSFET detectors; MOSFET dose (cGy), delivery time, and MU/cGy values were recorded. Maximum and mean dose deviations were calculated from MOSFET data. The number of MOSFETs with at least 19 of 20 detectors agreeing with their expected dose within 5% per fraction was calculated across 10 6 iterations to model dose deviation as function of fraction number for all plan variants. To put interplay plans into clinical context, additional IMRT and VMAT plans were created and delivered for the sites of head and neck, prostate, whole brain, breast, pelvis, and lung. Average modulation and interplay effect were compared to those from conventional linear accelerators, as reported from previous studies. The mean beam modulation for plans created for the Halcyon 1.0 linear accelerator was 2.9 MU/cGy (two- to four-field IMRT breast plans), 6.2 MU/cGy (at least five-field IMRT), and 3.6 MU/cGy (four-arc VMAT). To achieve treatment plan objectives, Halcyon 1.0 VMAT plans require more arcs and modulation than VMAT on conventional linear accelerators. Maximum and mean dose deviations increased with increasing plan complexity under tumor motion for breast and lung treatments. Concerning VMAT plans under motion, maximum, and mean dose deviations were higher for one arc than for two arcs regardless of plan complexity. For plan variants with maximum dose deviations greater than 3.7%, dose deviation as a function of fraction number was protracted. For treatments on the Halcyon 1.0 linear accelerator, the convergence of dose deviation with fraction number happened more slowly than reported for conventional linear accelerators. However, if plan complexity is reduced for IMRT and if tumor motion is less than ~10-mm, interplay is greatly reduced. To minimize dose deviations across multiple fractions for dynamic targets, we recommend limiting treatment plan complexity and avoiding one-arc VMAT on the Halcyon 1.0 linear accelerator when interplay is a concern. © 2018 American Association of Physicists in Medicine.

Simplified Solar Modulation Model of Inner Trapped Belt Proton Flux As a Function of Atmospheric Density

NASA Technical Reports Server (NTRS)

Wilson, Thomas L.; Lodhi, M. A. K.; Diaz, Abel B.

2005-01-01

No simple algorithm seems to exist for calculating proton fluxes and lifetimes in the Earth's inner, trapped radiation belt throughout the solar cycle. Most models of the inner trapped belt in use depend upon AP8 which only describes the radiation environment at solar maximum and solar minimum in Cycle 20. One exception is NOAAPRO which incorporates flight data from the TIROS/NOAA polar orbiting spacecraft. The present study discloses yet another, simple formulation for approximating proton fluxes at any time in a given solar cycle, in particular between solar maximum and solar minimum. It is derived from AP8 using a regression algorithm technique from nuclear physics. From flux and its time integral fluence, one can then approximate dose rate and its time integral dose. It has already been published in this journal that the absorbed dose rate, D, in the trapped belts exhibits a power law relationship, D = A(rho)(sup -n), where A is a constant, rho is the atmospheric density, and the index n is weakly dependent upon shielding. However, that method does not work for flux and fluence. Instead, we extend this idea by showing that the power law approximation for flux J is actually bivariant in energy E as well as density rho. The resulting relation is J(E,rho)approx.(sum of)A(E(sup n))rho(sup -n), with A itself a power law in E. This provides another method for calculating approximate proton flux and lifetime at any time in the solar cycle. These in turn can be used to predict the associated dose and dose rate.

POLYMERIZATION OF /cap alpha/-METHYLSTYRENE BY ELECTRON IRRADIATION (in German)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Braun, D.; Heufer, G.; Seufert, W.

1964-01-01

Ampoules of alpha -methylstyrene sealed under vacuum were irradiated with 1-Mev electrons in a type JS Van de Graaff generator; comparative experiments with gamma rays were carried out with a /sup 60/Co source of 3000 deg C. High doses of electrons (ca. 10/sup 8/ rad) are necessary for polymerization. The conversion is graphed as a function of dose at 0 deg C; it reaches a maximum plateau of 65% at 4 x 10/sup 8/ rad; this may point to radiolysis of the polymer at doses above this. Polymerization conversion increases with decreasing dose rate, when dose and temperature are heldmore » constant; and conversion increases with decreasing temperature (22% at --22 deg C; 10% at 15 deg C; <1% at 60 deg C), as has been found with gamma rays. In the solid state between --40 deg C and --80 deg C the maximum yield is only about 5%. The molecular weights of all poly- alpha -methylstyrenes thus formed lie between 3000 and 12,000, independently of dose rate and temperature. All polymethylstyrenes formed in the liquid state have approximately the same tacticity independent of temperature (isotactic about 20%; syndiotactic about 80%). This corresponds to the tacticity of polymers formed cationically with Lewis acids. In the solid state the tacticity is: isotactic 38%, syndiotactic, 62%, comparable with the tacticity of anionic polymerization. In the liquid state the tacticity and the sensitivity towards water indicate a cationic mechanism for the reaction. NMR studies also indicate a cationic mechanism. (BBB)« less

Relative dosimetrical verification in high dose rate brachytherapy using two-dimensional detector array IMatriXX

PubMed Central

Manikandan, A.; Biplab, Sarkar; David, Perianayagam A.; Holla, R.; Vivek, T. R.; Sujatha, N.

2011-01-01

For high dose rate (HDR) brachytherapy, independent treatment verification is needed to ensure that the treatment is performed as per prescription. This study demonstrates dosimetric quality assurance of the HDR brachytherapy using a commercially available two-dimensional ion chamber array called IMatriXX, which has a detector separation of 0.7619 cm. The reference isodose length, step size, and source dwell positional accuracy were verified. A total of 24 dwell positions, which were verified for positional accuracy gave a total error (systematic and random) of –0.45 mm, with a standard deviation of 1.01 mm and maximum error of 1.8 mm. Using a step size of 5 mm, reference isodose length (the length of 100% isodose line) was verified for single and multiple catheters of same and different source loadings. An error ≤1 mm was measured in 57% of tests analyzed. Step size verification for 2, 3, 4, and 5 cm was performed and 70% of the step size errors were below 1 mm, with maximum of 1.2 mm. The step size ≤1 cm could not be verified by the IMatriXX as it could not resolve the peaks in dose profile. PMID:21897562

Preliminary results of radiation measurements on EURECA

NASA Technical Reports Server (NTRS)

Benton, E. V.; Frank, A. L.

1995-01-01

The eleven-month duration of the EURECA mission allows long-term radiation effects to be studied similarly to those of the Long Duration Exposure Facility (LDEF). Basic data can be generated for projections to crew doses and electronic and computer reliability on spacecraft missions. A radiation experiment has been designed for EURECA which uses passive integrating detectors to measure average radiation levels. The components include a Trackoscope, which employs fourteen plastic nuclear track detector (PNTD) stacks to measure the angular dependence of high LET (greater than or equal to 6 keV/micro m) radiation. Also included are TLD's for total absorbed doses, thermal/resonance neutron detectors (TRND's) for low energy neutron fluences and a thick PNTD stack for depth dependence measurements. LET spectra are derived from the PNTD measurements. Preliminary TLD results from seven levels within the detector array show that integrated does inside the flight canister varied from 18.8 +/- 0.6 cGy to 38.9 +/- 1.2 cGy. The TLD's oriented toward the least shielded direction averaged 53% higher in dose than those oriented away from the least shielded direction (minimum shielding toward the least shielded direction varied from 1.13 to 7.9 g/cm(exp 2), Al equivalent). The maximum dose rate on EURECA (1.16 mGy/day) was 37% of the maximum measured on LDEF and dose rates at all depths were less than measured on LDEF. The shielding external to the flight canister covered a greater solid angle about the canister than the LDEF experiments.

System Design Verification for Closed Loop Control of Oxygenation With Concentrator Integration.

PubMed

Gangidine, Matthew M; Blakeman, Thomas C; Branson, Richard D; Johannigman, Jay A

2016-05-01

Addition of an oxygen concentrator into a control loop furthers previous work in autonomous control of oxygenation. Software integrates concentrator and ventilator function from a single control point, ensuring maximum efficiency by placing a pulse of oxygen at the beginning of the breath. We sought to verify this system. In a test lung, fraction of inspired oxygen (FIO2) levels and additional data were monitored. Tests were run across a range of clinically relevant ventilator settings in volume control mode, for both continuous flow and pulse dose flow oxygenation. Results showed the oxygen concentrator could maintain maximum pulse output (192 mL) up to 16 breaths per minute. Functionality was verified across ranges of tidal volumes and respiratory rates, with and without positive end-expiratory pressure, in continuous flow and pulse dose modes. For a representative test at respiratory rate 16 breaths per minute, tidal volume 550 mL, without positive end-expiratory pressure, pulse dose oxygenation delivered peak FIO2 of 76.83 ± 1.41%, and continuous flow 47.81 ± 0.08%; pulse dose flow provided a higher FIO2 at all tested setting combinations compared to continuous flow (p < 0.001). These tests verify a system that provides closed loop control of oxygenation while integrating time-coordinated pulse-doses from an oxygen concentrator. This allows the most efficient use of resources in austere environments. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

Evaluation of potential hazard exposure resulting from DOE waste treatment and disposal at Rollins Environmental Services, Baton Rouge, LA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1992-04-01

The equivalent dose rate to populations potentially exposed to wastes shipped to Rollins Environmental Services, Baton Rouge, LA from Oak Ridge and Savannah River Operations of the Department of Energy was estimated. Where definitive information necessary to the estimation of a dose rate was unavailable, bounding assumptions were employed to ensure an overestimate of the actual dose rate experienced by the potentially exposed population. On this basis, it was estimated that a total of about 3.85 million pounds of waste was shipped from these DOE operations to Rollins with a maximum combined total activity of about 0.048 Curies. Populations nearmore » the Rollins site could potentially be exposed to the radionuclides in the DOE wastes via the air pathway after incineration of the DOE wastes or by migration from the soil after landfill disposal. AIRDOS was used to estimate the dose rate after incineration. RESRAD was used to estimate the dose rate after landfill disposal. Calculations were conducted with the estimated radioactive specie distribution in the wastes and, as a test of the sensitivity of the results to the estimated distribution, with the entire activity associated with individual radioactive species such as Cs-137, Ba-137, Sr-90, Co-60, U-234, U-235 and U-238. With a given total activity, the dose rates to nearby individuals were dominated by the uranium species.« less

Biological X-ray irradiator characterization for use with small animals and cells.

PubMed

Bruno, A Colello; Mazaro, S J; Amaral, L L; Rego, E M; Oliveira, H F; Pavoni, J F

2017-03-02

This study presents the characterization of an X-ray irradiator through dosimetric tests, which confirms the actual dose rate that small animals and cells will be exposed to during radiobiological experiments. We evaluated the linearity, consistency, repeatability, and dose distribution in the positions in which the animals or cells are placed during irradiation. In addition, we evaluated the performance of the X-ray tube (voltage and tube operating current), the radiometric survey (leakage radiation) and safety devices. The irradiator default setting was established as 160 kV and 25 mA. Tests showed that the dose rate was linear overtime (R2=1) and remained stable for long (constant) and short (repeatability) intervals between readings. The mean dose rate inside the animal cages was 1.27±0.06 Gy/min with a uniform beam of 95.40% (above the minimum threshold guaranteed by the manufacturer). The mean dose rate inside the cell plates was 0.92±0.19 Gy/min. The dose rate dependence with tube voltage and current presented a quadratic and linear relationship, respectively. There was no observed mechanical failure during evaluation of the irradiator safety devices and the radiometric survey obtained a maximum ambient equivalent dose rate of 0.26 mSv/h, which exempts it from the radiological protection requirements of the International Atomic Energy Agency. The irradiator characterization enables us to perform radiobiological experiments, and assists or even replaces traditional therapy equipment (e.g., linear accelerators) for cells and small animal irradiation, especially in early research stages.

Development of a novel low-radiation-absorbent lok-bar to reduce X-ray scattering and absorption in RapidArc® treatment planning and dose delivery.

PubMed

Monzen, Hajime; Kubo, Kazuki; Tamura, Mikoto; Hayakawa, Masaru; Nishimura, Yasumasa

2017-05-01

We developed a novel low-radiation-absorbent lok-bar (HM-bar) that is used to secure the immobilizers to the couch. The aim of this study was to investigate the X-ray scattering and absorption properties of the HM-bar in computed tomography (CT) simulation and radiotherapy dose delivery using the Varian Exact™ lok-bar (VL-bar) as a benchmark. CT images were obtained with or without lok-bar, and then each image was visually evaluated for artifacts. The attenuation rates for each lok-bar were measured using a farmer-type ionization chamber (PTW30013) and the I'mRT phantom (IBA Dosimetry GmbH). Measurement points were between gantry angles of 110 and 180°. The treatment apparatus was a NovalisTx (Brainlab AG); X-ray energies were set at 6 MV and 10 MV. In the presence of each lok-bar, the radiation dose was measured in accordance with 10 volumetric modulated arc therapy-stereotactic body radiation therapy (VMAT-SBRT) plans for lung cancer. Artifacts were seldom observed in the CT scans of the HM-bar. The attenuation rate of each lok-bar was higher when the X-ray energy was set at 6 MV than at 10 MV. The highest attenuation rate in the VL-bar was observed at a gantry angle of 112°; the rates were 22.4% at 6 MV and 19.3% at 10 MV. Similarly, the highest attenuation rate for the HM-bar was also observed at a gantry angle of 112°; the rates were 12.2% and 10.1% at 6 MV and 10 MV, respectively. When the VL-bar was evaluated, the isocenter dose of the VMAT-SBRT plans was attenuated by 2.6% as a maximum case. In the case of the HM-bar, the maximum attenuation was 1.4%. In the measurements of each VMAT-SBRT plan, the difference of the dose attenuation rate between the VL-bar and HM-bar was approximately 1%. The HM-bar could be used to minimize the occurrence of artifacts and provide good images in CT scans regarding radiotherapy planning and dose calculation. It can be used for patient therapy at hospitals to provide accurate dose delivery because of its low X-ray scattering and absorption characteristics. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

SU-E-T-13: Comparison of Dose Rates with and without Gold Backing of USC #9 Radioactive Eye Plaque Using MCNP5.

PubMed

Aryal, P; Molloy, J

2012-06-01

To show the effect of gold backing on dose rates for the USC #9 radioactive eye plaque. An I125 source (IsoAid model IAI-125A) and gold backing was modeled using MCNP5 Monte Carlo code. A single iodine seed was simulated with and without gold backing. Dose rates were calculated in two orthogonal planes. Dose calculation points were structured in two orthogonal planes that bisect the center of the source. A 2×2 cm matrix of spherical points of radius 0.2 mm was created in a water phantom of 10 cm radius. 0.2 billion particle histories were tracked. Dose differences with and without the gold backing were analyzed using Matlab. The gold backing produced a 3% increase in the dose rate near the source surface (<1mm) relative to that without the backing. This was presumably caused by fluorescent photons from the gold. At distances between 1 and 2 cm, the gold backing reduced the dose rate by up to 12%, which we attribute to a lack of scatter resulting from the attenuation from the gold. Dose differences were most pronounced in the radial direction near the source center but off axis. The dose decreased by 25%, 65% and 81% at 1, 2, and 3 mm off axis at a distance of 1 mm from the source surface. These effects were less pronounced in the perpendicular dimension near the source tip, where maximum dose decreases of 2% were noted. I 125 sources embedded directly into gold troughs display dose differences of 2 - 90%, relative to doses without the gold backing. This is relevant for certain types of plaques used in treatment of ocular melanoma. Large dose reductions can be observed and may have implications for scleral dose reduction. © 2012 American Association of Physicists in Medicine.

Ion-recombination correction for different ionization chambers in high dose rate flattening-filter-free photon beams

NASA Astrophysics Data System (ADS)

Lang, Stephanie; Hrbacek, Jan; Leong, Aidan; Klöck, Stephan

2012-05-01

Recently, there has been an increased interest in flattening-filter-free (FFF) linear accelerators. Removal of the filter results in available dose rates up to 24 Gy min-1 (for nominal energy 10 MV in depth of maximum dose, a source-surface distance of 100 cm and a field size of 10×10 cm2). To guarantee accurate relative and reference dosimetry for the FFF beams, we investigated the charge collection efficiency of multiple air-vented and one liquid ionization chamber for dose rates up to 31.9 Gy min-1. For flattened beams, the ion-collection efficiency of all air-vented ionization chambers (except for the PinPoint chamber) was above 0.995. By removing the flattening filter, we found a reduction in collection efficiency of approximately 0.5-0.9% for a 10 MV beam. For FFF beams, the Markus chamber showed the largest collection efficiency of 0.994. The observed collection efficiencies were dependent on dose per pulse, but independent of the pulse repetition frequency. Using the liquid ionization chamber, the ion-collection efficiency for flattened beams was above 0.990 for all dose rates. However, this chamber showed a low collection efficiency of 0.940 for the FFF 10 MV beam at a dose rate of 31.9 Gy min-1. All investigated air-vented ionization chambers can be reliably used for relative dosimetry of FFF beams. The order of correction for reference dosimetry is given in the manuscript. Due to their increased saturation in high dose rate FFF beams, liquid ionization chambers appear to be unsuitable for dosimetry within these contexts.

Effects of a prostagrandin EP4-receptor agonist ONO-AE1-329 on the left ventricular pressure-volume relationship in the halothane-anesthetized dogs.

PubMed

Honda, Atsushi; Nakamura, Yuji; Ohara, Hiroshi; Cao, Xin; Nomura, Hiroaki; Katagi, Jun; Wada, Takeshi; Izumi-Nakaseko, Hiroko; Ando, Kentaro; Sugiyama, Atsushi

2016-03-15

Cardiac effects of a prostagrandin EP4-receptor agonist ONO-AE1-329 were assessed in the halothane-anesthetized dogs under the monitoring of left ventricular pressure-volume relationship, which were compared with those of clinically recommended doses of dopamine, dobutamine and milrinone (n=4-5 for each treatment). ONO-AE1-329 was intravenously administered in doses of 0.3, 1 and 3 ng/kg/min for 10 min with a pause of 20 min. Dopamine in a dose of 3 µg/kg/min for 10 min, dobutamine in a dose of 1 µg/kg/min for 10 min and milrinone in a dose of 5 µg/kg/min for 10 min followed by 0.5 µg/kg/min for 10 min were intravenously administered. Low dose of ONO-AE1-329 increased the stroke volume. Middle dose of ONO-AE1-329 increased the cardiac output, left ventricular end-diastolic volume, ejection fraction, maximum upstroke/downstroke velocities of the left ventricular pressure and external work, but decreased the end-systolic pressure and internal work besides the change by the low dose. High dose of ONO-AE1-329 increased the heart rate and maximum elastance, but decreased the end-systolic volume besides the changes by the middle dose. Dopamine, dobutamine and milrinone exerted essentially similar cardiac effects to ONO-AE1-329, but they did not significantly change the end-diastolic volume, end-systolic volume, stroke volume, ejection fraction, end-systolic pressure, maximum elastance, external work or internal work. Thus, EP4-receptor stimulation by ONO-AE1-329 may have potential to better promote the passive ventricular filling than the conventional cardiotonic drugs, which could become a candidate of novel therapeutic strategy for the treatment of heart failure with preserved ejection fraction. Copyright © 2016 Elsevier B.V. All rights reserved.

Skyshine photon doses from 6 and 10 MV medical linear accelerators.

PubMed

de Paiva, Eduardo; da Rosa, Luiz A R

2012-01-05

The skyshine radiation phenomenon consists of the scattering of primary photon beams in the atmosphere above the roof of a medical linear accelerator facility, generating an additional dose at ground level in the vicinity of the treatment room. Thus, with respect to radioprotection, this situation plays an important role when the roof is designed with little shielding and there are buildings next to the radiotherapy treatment room. In literature, there are few reported skyshine-measured doses and these contain poor agreement with empirical calculations. In this work, we carried out measurements of skyshine photon dose rates produced from eight different 6 and 10 MV medical accelerators. Each measurement was performed outside the room facility, with the beam positioned in the upward direction, at a horizontal distance from the target and for a 40 cm × 40 cm maximum photon field size at the accelerator isocenter. Measured dose-equivalent rates results were compared with calculations obtained by an empirical expression, and differences between them deviated in one or more order of magnitude.

Safety and tolerability of ibrutinib monotherapy in Japanese patients with relapsed/refractory B cell malignancies.

PubMed

Tobinai, Kensei; Ogura, Michinori; Ishizawa, Kenichi; Suzuki, Tatsuya; Munakata, Wataru; Uchida, Toshiki; Aoki, Tomohiro; Morishita, Takanobu; Ushijima, Yoko; Takahara, Satoko

2016-01-01

In this phase I dose-escalation study we evaluated the safety, tolerability, pharmacokinetics, and antitumor activity of ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase (BTK, in Japanese patients with relapsed/refractory B cell malignancies (RRBCM). Fifteen patients aged 42-78 years were enrolled to one of three cohorts. Cohort 1 (n = 3) consisted of two phases, a single-dose (140 and 280 mg) phase and a multiple-dose (420 mg) phase of ibrutinib; cohort 2 (n = 6) included multiple doses of ibrutinib 560 mg; and cohort 3 (n = 6) included only patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) dosed at ibrutinib 420 mg. One patient (CLL/SLL cohort) experienced grade 3 pneumonia and sepsis, which were considered dose-limiting toxicities. No deaths were reported. The most common (≥ 20% patients) adverse events were neutropenia, anemia, nasopharyngitis, increased bilirubin, and rash. Dose-dependent increase in maximum plasma concentration and area under the concentration from 0 to the last quantifiable time was observed, while time to reach maximum plasma concentration and elimination half-life was similar between doses. The overall response rate was 73.3% (11/15) for all cohorts combined. Overall, ibrutinib (420 and 560 mg) was tolerable with acceptable safety profiles and effective for Japanese patients with RRBCM including CLL/SLL. NCT01704963.

Is volumetric modulated arc therapy with constant dose rate a valid option in radiation therapy for head and neck cancer patients?

PubMed

Didona, Annamaria; Lancellotta, Valentina; Zucchetti, Claudio; Panizza, Bianca Moira; Frattegiani, Alessandro; Iacco, Martina; Di Pilato, Anna Concetta; Saldi, Simonetta; Aristei, Cynthia

2018-01-01

Intensity-modulated radiotherapy (IMRT) improves dose distribution in head and neck (HN) radiation therapy. Volumetric-modulated arc therapy (VMAT), a new form of IMRT, delivers radiation in single or multiple arcs, varying dose rates (VDR-VMAT) and gantry speeds, has gained considerable attention. Constant dose rate VMAT (CDR-VMAT) associated with a fixed gantry speed does not require a dedicated linear accelerator like VDR-VMAT. The present study explored the feasibility, efficiency and delivery accuracy of CDR-VMAT, by comparing it with IMRT and VDR-VMAT in treatment planning for HN cancer. Step and shoot IMRT (SS-IMRT), CDR-VMAT and VDR-VMAT plans were created for 15 HN cancer patients and were generated by Pinnacle 3 TPS (v 9.8) using 6 MV photon energy. Three PTVs were defined to receive respectively prescribed doses of 66 Gy, 60 Gy and 54 Gy, in 30 fractions. Organs at risk (OARs) included the mandible, spinal cord, brain stem, parotids, salivary glands, esophagus, larynx and thyroid. SS-IMRT plans were based on 7 co-planar beams at fixed gantry angles. CDR-VMAT and VDR-VMAT plans, generated by the SmartArc module, used a 2-arc technique: one clockwise from 182° to 178° and the other one anti-clockwise from 178° to 182°. Comparison parameters included dose distribution to PTVs ( D mean , D 2% , D 50% , D 95% , D 98% and Homogeneity Index), maximum or mean doses to OARs, specific dose-volume data, the monitor units and treatment delivery times. Compared with SS-IMRT, CDR-VMAT significantly reduced the maximum doses to PTV1 and PTV2 and significantly improved all PTV3 parameters, except D 98% and D 95% . It significantly spared parotid and submandibular glands and was associated with a lower D mean to the larynx. Compared with VDR-VMAT, CDR-VMAT was linked to a significantly better D mean , to the PTV3 but results were worse for the parotids, left submandibular gland, esophagus and mandible. Furthermore, the D mean to the larynx was also worse. Compared with SS-IMRT and VDR-VMAT, CDR-VMAT was associated with higher average monitor unit values and significantly shorter average delivery times. CDR-VMAT appeared to be a valid option in Radiation Therapy Centers that lack a dedicated linear accelerator for volumetric arc therapy with variable dose-rates and gantry velocities, and are unwilling or unable to sanction major expenditure at present but want to adopt volumetric techniques.

A phase I study of OSI-461 in combination with mitoxantrone in patients with advanced solid tumors potentially responsive to mitoxantrone

PubMed Central

Resta, Lee P.; Pili, Roberto; Eisenberger, Mario A.; Spitz, Avery; King, Serina; Porter, Jennifer; Franke, Amy; Boinpally, Ramesh; Sweeney, Christopher J.

2010-01-01

Purpose To find the maximum tolerated dose (MTD) of OSI-461 in combination with mitoxantrone in patients with advanced solid tumors. Methods This was a Phase I study using cohort dose escalation of OSI-461 dosed orally twice daily in combination with mitoxantrone 12 mg/m2 given on Day 1 of each 21-day cycle. Results OSI-461 dose was escalated to 1,000 mg po bid. One patient experienced a dose-limiting toxicity (DLT). Three patients discontinued the study due to adverse events (AE). Two patients (10%) had a partial response, and ten patients (50%) had stable disease as best response. Conclusion The combination of OSI-461 and mitoxantrone was well tolerated. Dose escalation was stopped because of toxicities in a concurrent Phase I trial. The response rate seen in patients with prostate cancer was comparable to response rates seen in trials of mitoxantrone and prednisone alone, and further studies of the combination of OSI-461 and mitoxantrone were not pursued. PMID:20445979

NIRS external dose estimation system for Fukushima residents after the Fukushima Dai-ichi NPP accident

NASA Astrophysics Data System (ADS)

Akahane, Keiichi; Yonai, Shunsuke; Fukuda, Shigekazu; Miyahara, Nobuyuki; Yasuda, Hiroshi; Iwaoka, Kazuki; Matsumoto, Masaki; Fukumura, Akifumi; Akashi, Makoto

2013-04-01

The great east Japan earthquake and subsequent tsunamis caused Fukushima Dai-ichi Nuclear Power Plant (NPP) accident. National Institute of Radiological Sciences (NIRS) developed the external dose estimation system for Fukushima residents. The system is being used in the Fukushima health management survey. The doses can be obtained by superimposing the behavior data of the residents on the dose rate maps. For grasping the doses, 18 evacuation patterns of the residents were assumed by considering the actual evacuation information before using the survey data. The doses of the residents from the deliberate evacuation area were relatively higher than those from the area within 20 km radius. The estimated doses varied from around 1 to 6 mSv for the residents evacuated from the representative places in the deliberate evacuation area. The maximum dose in 18 evacuation patterns was estimated to be 19 mSv.

NIRS external dose estimation system for Fukushima residents after the Fukushima Dai-ichi NPP accident.

PubMed

Akahane, Keiichi; Yonai, Shunsuke; Fukuda, Shigekazu; Miyahara, Nobuyuki; Yasuda, Hiroshi; Iwaoka, Kazuki; Matsumoto, Masaki; Fukumura, Akifumi; Akashi, Makoto

2013-01-01

The great east Japan earthquake and subsequent tsunamis caused Fukushima Dai-ichi Nuclear Power Plant (NPP) accident. National Institute of Radiological Sciences (NIRS) developed the external dose estimation system for Fukushima residents. The system is being used in the Fukushima health management survey. The doses can be obtained by superimposing the behavior data of the residents on the dose rate maps. For grasping the doses, 18 evacuation patterns of the residents were assumed by considering the actual evacuation information before using the survey data. The doses of the residents from the deliberate evacuation area were relatively higher than those from the area within 20 km radius. The estimated doses varied from around 1 to 6 mSv for the residents evacuated from the representative places in the deliberate evacuation area. The maximum dose in 18 evacuation patterns was estimated to be 19 mSv.

SU-F-T-113: Inherent Functional Dependence of Spinal Cord Doses of Variable Irradiated Volumes in Spine SBRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, L; Braunstein, S; Chiu, J

2016-06-15

Purpose: Spinal cord tolerance for SBRT has been recommended for the maximum point dose level or at irradiated volumes such as 0.35 mL or 10% of contoured volumes. In this study, we investigated an inherent functional relationship that associates these dose surrogates for irradiated spinal cord volumes of up to 3.0 mL. Methods: A hidden variable termed as Effective Dose Radius (EDR) was formulated based on a dose fall-off model to correlate dose at irradiated spinal cord volumes ranging from 0 mL (point maximum) to 3.0 mL. A cohort of 15 spine SBRT cases was randomly selected to derive anmore » EDR-parameterized formula. The mean prescription dose for the studied cases was 21.0±8.0 Gy (range, 10–40Gy) delivered in 3±1 fractions with target volumes of 39.1 ± 70.6 mL. Linear regression and variance analysis were performed for the fitting parameters of variable EDR values. Results: No direct correlation was found between the dose at maximum point and doses at variable spinal cord volumes. For example, Pearson R{sup 2} = 0.643 and R{sup 2}= 0.491 were obtained when correlating the point maximum dose with the spinal cord dose at 1 mL and 3 mL, respectively. However, near perfect correlation (R{sup 2} ≥0.99) was obtained when corresponding parameterized EDRs. Specifically, Pearson R{sup 2}= 0.996 and R{sup 2} = 0.990 were obtained when correlating EDR (maximum point dose) with EDR (dose at 1 mL) and EDR(dose at 3 mL), respectively. As a result, high confidence level look-up tables were established to correlate spinal cord doses at the maximum point to any finite irradiated volumes. Conclusion: An inherent functional relationship was demonstrated for spine SBRT. Such a relationship unifies dose surrogates at variable cord volumes and proves that a single dose surrogate (e.g. point maximum dose) is mathematically sufficient in constraining the overall spinal cord dose tolerance for SBRT.« less

SU-E-T-145: Beam Characteristics of Flattening Filter Free Beams Including Low Dose Rate Setting

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uehara, K; Ogata, T; Nakayama, M

2015-06-15

Purpose: In commissioning of volumetric modulated arc therapy (VMAT), it is necessary to evaluate the beam characteristics of various dose rate settings with potential to use. The aim of this study is to evaluate the beam characteristics of flattened and flattening filter free (FFF) including low dose rate setting. Methods: We used a Varian TrueBeam with Millennium 120 MLC. Both 6 and 10 MV beams with or without flattening filter were used for this study. To evaluate low-dose rate FFF beams, specially-designed leaf sequence files control out-of-field MLC leaf pair at constant dose rate ranging from 80 to 400 MU/min.more » For dose rate from 80 MU/min to the maximum usable value of all energies, beam output were measured using ionization chamber (CC04, IBA). The ionization chamber was inserted into water equivalent phantom (RT3000-New, R-tech), and the phantom was set with SAD of 100cm. The beam profiles were performed using the 2D diode array (Profiler2, Sun Nuclear). The SSD was set to 90cm and a combined 30cmx30cmx9cm phantom which consisted of solid water slabs was put on the device. All measurement were made using 100MU irradiation for 10cmx10cm jaw-defined field size with a gantry angle of 0°. Results: In all energies, the dose rate dependences with beam output and variation coefficient were within 0.2% and 0.07%, respectively. The flatness and symmetry exhibited small variations (flatness ≤0.1 point and symmetry≤0.3 point at absolute difference). Conclusion: We had studied the characteristics of flattened and FFF beam over the 80 MU/min. Our results indicated that the beam output and profiles of FFF of TrueBeam linac were highly stable at low dose rate setting.« less

Passive dosimetry aboard the Mir Orbital Station: internal measurements.

PubMed

Benton, E R; Benton, E V; Frank, A L

2002-10-01

Passive radiation dosimeters were exposed aboard the Mir Orbital Station over a substantial portion of the solar cycle in order to measure the change in dose and dose equivalent rates as a function of time. During solar minimum, simultaneous measurements of the radiation environment throughout the habitable volume of the Mir were made using passive dosimeters in order to investigate the effect of localized shielding on dose and dose equivalent. The passive dosimeters consisted of a combination of thermoluminescent detectors to measure absorbed dose and CR-39 PNTDs to measure the linear energy transfer (LET) spectrum from charged particles of LET infinity H2O > or = 5 keV/micrometers. Results from the two detector types were then combined to yield mean total dose rate, mean dose equivalent rate, and average quality factor. Contrary to expectations, both dose and dose equivalent rates measured during May-October 1991 near solar maximum were higher than similar measurements carried out in 1996-1997 during solar minimum. The elevated dose and dose equivalent rates measured in 1991 were probably due to a combination of intense solar activity, including a large solar particle event on 9 June 1991, and the temporary trapped radiation belt created in the slot region by the solar particle event and ensuing magnetic storm of 24 March 1991. During solar minimum, mean dose and dose equivalent rates were found to vary by factors of 1.55 and 1.37, respectively, between different locations through the interior of Mir. More heavily shielded locations tended to yield lower total dose and dose equivalent rates, but higher average quality factor than did more lightly shielding locations. However, other factors such as changes in the immediate shielding environment surrounding a given detector location, changes in the orientation of the Mir relative to its velocity vector, and changes in the altitude of the station also contributed to the variation. Proton and neutron-induced target fragment secondaries, not primary galactic cosmic rays, were found to dominate the LET spectrum above 100 keV/micrometers. This indicates that in low earth orbit, trapped protons in the South Atlantic Anomaly are responsible for the major fraction of the total dose equivalent. c2002 Elsevier Science Ltd. All rights reserved.

Safety, tolerability, pharmacokinetics and pharmacodynamics of single doses of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in healthy Japanese subjects.

PubMed

Sarashina, Akiko; Koiwai, Kazuki; Seman, Leo J; Yamamura, Norio; Taniguchi, Atsushi; Negishi, Takahiro; Sesoko, Shogo; Woerle, Hans J; Dugi, Klaus A

2013-01-01

This randomized, placebo-controlled within dose groups, double-blind, single rising dose study investigated the safety, tolerability, pharmacokinetics and pharmacodynamics of 1 mg to 100 mg doses of empagliflozin in 48 healthy Japanese male subjects. Empagliflozin was rapidly absorbed, reaching peak levels in 1.25 to 2.50 h; thereafter, plasma concentrations declined in a biphasic fashion, with mean terminal elimination half-life ranging from 7.76 to 11.7 h. Increase in empagliflozin exposure was proportional to dose. Oral clearance was dose independent and ranged from 140 to 172 mL/min. In the 24 h following 100 mg empagliflozin administration, the mean (%CV) amount of glucose excreted in urine was 74.3 (17.1) g. The amount and the maximum rate of glucose excreted via urine increased with dose of empagliflozin. Nine adverse events, all of mild intensity, were reported by 8 subjects (7 with empagliflozin and 1 with the placebo). No hypoglycemia was reported. In conclusion, 1 mg to 100 mg doses of empagliflozin had a good safety and tolerability profile in healthy Japanese male subjects. Exposure to empagliflozin was dose proportional. The amount and rate of urinary glucose excretion were higher with empagliflozin than with the placebo, and increased with empagliflozin dose.

Near infrared radio-luminescence of O{sub 2} loaded radiation hardened silica optical fibers: A candidate dosimeter for harsh environments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Di Francesca, D., E-mail: diego.di.francesca@univ-st-etienne.fr; Dipartimento di Fisica e Chimica, Università degli Studi di Palermo, I-90123 Palermo; Girard, S.

2014-11-03

We report on an experimental investigation of the infrared Radio-Luminescence (iRL) emission of interstitial O{sub 2} molecules loaded in radiation hardened pure-silica-core and fluorine-doped silica-based optical fibers (OFs). The O{sub 2} loading treatment successfully dissolved high concentrations of oxygen molecules into the silica matrix. A sharp luminescence at 1272 nm was detected when 2.5 cm of the treated OFs were irradiated with 10 keV X-rays. This emission originates from the radiative decay of the first excited singlet state of the embedded O{sub 2} molecules. The dose, dose-rate, and temperature dependencies of the infrared emission are studied through in situ optical measurements. The resultsmore » show that the iRL is quite stable in doses of up to 1 MGy(SiO{sub 2}) and is linearly dependent on the dose-rate up to the maximum investigated dose-rate of ∼200 kGy(SiO{sub 2})/h. The temperature dependency of the iRL shows a decrease in efficiency above 200 °C, which is attributed to the non-radiative decay of the excited O{sub 2} molecules. The results obtained and the long-term stability of the O{sub 2}-loading treatment (no out-gassing effect) strongly suggest the applicability of these components to real-time remote dosimetry in environments characterized by high radiation doses and dose-rates.« less

Radiation experiments on Cosmos 2044: K-7-41, parts A, B, C, D, E

NASA Technical Reports Server (NTRS)

Frank, A. L.; Benton, E. V.; Benton, E. R.; Dudkin, V. E.; Marenny, A. M.

1990-01-01

The Cosmos 2044 biosatellite mission offered the opportunity for radiation measurements under conditions which are seldom available (an inclination of 82.3 deg and attitude of 294 x 216 km). Measurements were made on the outside of the spacecraft under near-zero shielding conditions. Also, this mission was the first in which active temperature recorders (the ATR-4) were flown to record the temperature profiles of detector stacks. Measurements made on this mission provide a comparison and test for modeling of depth doses and LET spectra for orbital parameters previously unavailable. Tissue absorbed doses from 3480 rad (252 rad/d) down to 0.115 rad (8.33 mrad/d) were measured at different depths (0.0146 and 3.20 g/sq cm, respectively) with averaged TLD readings. The LET spectra yielded maximum and minimum values of integral flux of 27.3 x 10(exp -4) and 3.05 x 10(exp -4)/sq cm/s/sr, of dose rate of 7.01 and 1.20 mrad/d, and of dose equivalent rate of 53.8 and 11.6 mrem/d, for LET(sub infinity)-H2O is greater than or equal to 4 keV/micron. Neutron measurements yielded 0.018 mrem/d in the thermal region, 0.25 mrem/d in the resonance region and 3.3 mrem/d in the high energy region. The TLD depth dose and LET spectra were compared with calculations from the modeling codes. The agreement is good but some further refinements are in order. In comparing measurements on Cosmos 2044 with those from previous Cosmos missions (orbital inclinations of 62.8 deg) there is a greater spread (maximum to minimum) in depth doses and an increased contribution from GCRs, and higher LET particles, in the heavy particle fluxes.

Phase II Dose Escalation Study of Caspofungin for Invasive Aspergillosis ▿ §

PubMed Central

Cornely, O. A.; Vehreschild, J. J.; Vehreschild, M. J. G. T.; Würthwein, G.; Arenz, D.; Schwartz, S.; Heussel, C. P.; Silling, G.; Mahne, M.; Franklin, J.; Harnischmacher, U.; Wilkens, A.; Farowski, F.; Karthaus, M.; Lehrnbecher, T.; Ullmann, A. J.; Hallek, M.; Groll, A. H.

2011-01-01

Our objective was to evaluate the maximum tolerated dose of caspofungin for invasive aspergillosis (IA). The safety and pharmacokinetics of escalating dosages of caspofungin were investigated in IA. Eight patients each received caspofungin 70, 100, 150, or 200 mg once a day (QD). Dose-limiting toxicity (DLT) was defined as the same non-hematological treatment-related adverse event of grade ≥4 in 2 of 8 patients or ≥3 in 4 of 8 patients in a cohort. A total of 46 patients (median age, 61 years; 21 female; 89% with hematological malignancies) received caspofungin (9, 8, 9, and 20 patients in the 70-, 100-, 150-, and 200-mg cohorts) for a median of 24.5 days. Plasma pharmacokinetics were linear across the investigated dosages and followed a two-compartment model, with weight as the covariate on clearance and sex as the covariate on central volume of distribution. Simulated peak plasma concentrations at steady state ranged from 14.2 to 40.6 mg/liter (28%), trough concentrations from 4.1 to 11.8 mg/liter (58%), and area under the concentration-time curve from 175 to 500 mg/liter/h (32%) (geometric mean, geometric coefficient of variation). Treatment was well tolerated without dose-limiting toxicity. The rate of complete or partial responses was 54.3%, and the overall mortality at 12-week follow-up was 28.3%. In first-line treatment of invasive aspergillosis, daily doses of up to 200 mg caspofungin were well tolerated and the maximum tolerated dose was not reached. Pharmacokinetics was linear. Response rates were similar to those previously reported for voriconazole and liposomal amphotericin. PMID:21911573

Experiment K-7-41: Radiation Experiments on Cosmos 2044

NASA Technical Reports Server (NTRS)

Benton, E. V.; Benton, E. R.; Frank, A. L.; Dudkin, V. E.; Marenny, A. M.; Kovalev, E. E.

1994-01-01

The Cosmos 2044 biosatellite mission offered the opportunity for radiation measurements under conditions which are seldom available (an inclination of 82.3 degrees and altitude of 294 x 216 km). Measurements were made on the outside of the spacecraft under near-zero shielding conditions. Also, this mission was the first in which active temperature recorders (the ATR-4) were flown to record the temperature profiles of detector stacks. Measurements made on this mission provide a comparison and test for modeling of depth doses and LET spectra for orbital parameters previously unavailable. Tissue absorbed doses from 3480 rad (252 rad/d) down to 0.115 rad (8.33 mrad/d) were measured at different depths (0.0146 and 3.20 g/sq. cm, respectively) with averaged TLD readings. The LET spectra yielded maximum and minimum values of integral flux of 27.3 x 10-4 and 3.05 x 10(exp -4) cm(exp -2).s(exp -1).sr(exp -4) of dose rate of 7.01 and 1.20 mrad/d, and of dose equivalent rate of 53.8 and 11.6 mrem/d, for LET(infinity).H2O is greater than or equal to 4 keV/micro-m. Neutron measurements yielded 0.018 mremld in the thermal region, 0.25 mrem/d in the resonance region and 3.3 mrem/d in the high energy region. The TLD depth dose and LET spectra have been compared with calculations from the modeling codes. The agreement is good but some further refinements are in order. In comparing measurements on Cosmos 2044 with those from previous Cosmos missions (orbital inclinations of 62.8 degrees) there is a greater spread (maximum to minimum) in depth doses and an increased contribution from GCR's, and higher LET particles, in the heavy particle fluxes.

Solar Modulation of Inner Trapped Belt Radiation Flux as a Function of Atmospheric Density

NASA Technical Reports Server (NTRS)

Lodhi, M. A. K.

2005-01-01

No simple algorithm seems to exist for calculating proton fluxes and lifetimes in the Earth's inner, trapped radiation belt throughout the solar cycle. Most models of the inner trapped belt in use depend upon AP8 which only describes the radiation environment at solar maximum and solar minimum in Cycle 20. One exception is NOAAPRO which incorporates flight data from the TIROS/NOAA polar orbiting spacecraft. The present study discloses yet another, simple formulation for approximating proton fluxes at any time in a given solar cycle, in particular between solar maximum and solar minimum. It is derived from AP8 using a regression algorithm technique from nuclear physics. From flux and its time integral fluence, one can then approximate dose rate and its time integral dose.

Systemic Delivery of Atropine Sulfate by the MicroDose Dry-Powder Inhaler

PubMed Central

Venkataramanan, R.; Hoffman, R.M.; George, M.P.; Petrov, A.; Richards, T.; Zhang, S.; Choi, J.; Gao, Y.Y.; Oakum, C.D.; Cook, R.O.; Donahoe, M.

2013-01-01

Abstract Background Inhaled atropine is being developed as a systemic and pulmonary treatment for the extended recovery period after chemical weapons exposure. We performed a pharmacokinetics study comparing inhaled atropine delivery using the MicroDose Therapeutx Dry Powder Inhaler (DPIA) with intramuscular (IM) atropine delivery via auto-injector (AUTO). Methods The MicroDose DPIA utilizes a novel piezoelectric system to aerosolize drug and excipient from a foil dosing blister. Subjects inhaled a 1.95-mg atropine sulfate dose from the dry powder inhaler on one study day [5 doses×0.4 mg per dose (nominal) delivered over 12 min] and received a 2-mg IM injection via the AtroPen® auto-injector on another. Pharmacokinetics, pharmacodynamic response, and safety were studied for 12 hr. Results A total of 17 subjects were enrolled. All subjects completed IM dosing. One subject did not perform inhaled delivery due to a skin reaction from the IM dose. Pharmacokinetic results were as follows: area under the curve concentration, DPIA=20.1±5.8, AUTO=23.7±4.9 ng hr/mL (means±SD); maximum concentration reached, DPIA=7.7±3.5, AUTO=11.0±3.8 ng/mL; time to reach maximum concentration, DPIA=0.25±0.47, AUTO=0.19±0.23 hr. Pharmacodynamic results were as follows: maximum increase in heart rate, DPIA=18±12, AUTO=23±13 beats/min; average change in 1-sec forced expiratory volume at 30 min, DPIA=0.16±0.22 L, AUTO=0.11±0.29 L. The relative bioavailability for DPIA was 87% (based on output dose). Two subjects demonstrated allergic responses: one to the first dose (AUTO), which was mild and transient, and one to the second dose (DPIA), which was moderate in severity, required treatment with oral and intravenous (IV) diphenhydramine and IV steroids, and lasted more than 7 days. Conclusions Dry powder inhalation is a highly bioavailable route for attaining rapid and consistent systemic concentrations of atropine. PMID:22691110

Systemic delivery of atropine sulfate by the MicroDose Dry-Powder Inhaler.

PubMed

Corcoran, T E; Venkataramanan, R; Hoffman, R M; George, M P; Petrov, A; Richards, T; Zhang, S; Choi, J; Gao, Y Y; Oakum, C D; Cook, R O; Donahoe, M

2013-02-01

Inhaled atropine is being developed as a systemic and pulmonary treatment for the extended recovery period after chemical weapons exposure. We performed a pharmacokinetics study comparing inhaled atropine delivery using the MicroDose Therapeutx Dry Powder Inhaler (DPIA) with intramuscular (IM) atropine delivery via auto-injector (AUTO). The MicroDose DPIA utilizes a novel piezoelectric system to aerosolize drug and excipient from a foil dosing blister. Subjects inhaled a 1.95-mg atropine sulfate dose from the dry powder inhaler on one study day [5 doses × 0.4 mg per dose (nominal) delivered over 12 min] and received a 2-mg IM injection via the AtroPen® auto-injector on another. Pharmacokinetics, pharmacodynamic response, and safety were studied for 12 hr. A total of 17 subjects were enrolled. All subjects completed IM dosing. One subject did not perform inhaled delivery due to a skin reaction from the IM dose. Pharmacokinetic results were as follows: area under the curve concentration, DPIA=20.1±5.8, AUTO=23.7±4.9 ng hr/mL (means±SD); maximum concentration reached, DPIA=7.7±3.5, AUTO=11.0±3.8 ng/mL; time to reach maximum concentration, DPIA=0.25±0.47, AUTO=0.19±0.23 hr. Pharmacodynamic results were as follows: maximum increase in heart rate, DPIA=18±12, AUTO=23±13 beats/min; average change in 1-sec forced expiratory volume at 30 min, DPIA=0.16±0.22 L, AUTO=0.11±0.29 L. The relative bioavailability for DPIA was 87% (based on output dose). Two subjects demonstrated allergic responses: one to the first dose (AUTO), which was mild and transient, and one to the second dose (DPIA), which was moderate in severity, required treatment with oral and intravenous (IV) diphenhydramine and IV steroids, and lasted more than 7 days. Dry powder inhalation is a highly bioavailable route for attaining rapid and consistent systemic concentrations of atropine.

Evaluation of dose-response relationship between smoking load and cardiopulmonary fitness in adult smokers: A cross-sectional study.

PubMed

Lauria, V T; Sperandio, E F; de Sousa, T L W; de Oliveira Vieira, W; Romiti, M; de Toledo Gagliardi, A R; Arantes, R L; Dourado, V Z

To evaluate the dose-response relationship between smoking load and cardiopulmonary fitness, as measured with cardiopulmonary exercise testing (CPET), in adult smokers free of respiratory diseases. After a complete clinical evaluation and spirometry, 95 adult smokers (35 men and 60 women) underwent CPET on a treadmill. The physiological responses during CPET showed lower cardiorespiratory fitness levels, regardless of smoking load, with a peak [Formula: see text] lower than 100% of the expected value and a lower maximum heart rate. We observed a significant moderate negative correlation between smoking load and peak [Formula: see text] . The smoking load also presented a significant negative correlation with maximum heart rate(r=-0.36; p<0.05), lactate threshold(r=-0.45; p<0.05), and peak ventilation(r=-0.43; p<0.05). However, a dose-response relationship between smoking load quartiles and cardiopulmonary fitness was not found comparing quartiles of smoking loads after adjustment for age, sex and cardiovascular risk. There appears to be no dose-response relationship between SL and cardiopulmonary fitness in adult smokers with preserved pulmonary function, after adjusting the analysis for age and cardiovascular risk. Our results suggest that smoking cessation might be useful as the primary strategy to prevent cardiopulmonary fitness decline in smokers, regardless of smoking load. Thus, even a very low dose of tobacco use must be avoided in preventive strategies focusing on becoming people more physically active and fit. Copyright © 2016 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.

High dose rates obtained outside ISS in June 2015 during SEP event

NASA Astrophysics Data System (ADS)

Dachev, T. P.; Tomov, B. T.; Matviichuk, Yu. N.; Dimitrov, Pl. G.; Bankov, N. G.

2016-06-01

The R3DR2 instrument performed measurements in the European Space Agency (ESA) EXPOSE-R2 platform outside the Russian "Zvezda" module of the International Space Station (ISS) in the period 24 October 2014-11 January 2016. It is the Liulin-type deposited energy spectrometer (DES) (Dachev et al., 2015a). Took place in November 2014, this was the first attempt to monitor a small solar energetic particle (SEP) event outside ISS using the Liulin-type DES (Dachev et al., 2015d). In this study, we describe the dosimetric characteristics of the largest SEP event, observed on 22 June 2015 with the R3DR2 instrument outside ISS. The main finding of this study is that SEP protons with a minimum energy of approximately 7 MeV at the surface of the R3DR2 detector produced high dose rates, reaching >5000 μGy h-1, while the inner radiation belt maximum dose was at the level of 2200 μGy h-1. If a virtual external vehicle activity (EVA) was performed in the same period of the SEP maximum on 22 June 2015, the doses obtained in the skin of cosmonauts/astronauts can reach 2.84 mGy after 6.5 h, which is similar to the average absorbed dose inside ISS for 15 days (Reitz et al., 2005). A comparison with other extreme events measured with Liulin-type instruments shows that SEPs similar to that observed on 22 June 2015 could be one of the most dangerous events for the cosmonauts/astronauts involved in EVA.

Estimation of absorbed radiation dose rates in wild rodents inhabiting a site severely contaminated by the Fukushima Dai-ichi nuclear power plant accident.

PubMed

Kubota, Yoshihisa; Takahashi, Hiroyuki; Watanabe, Yoshito; Fuma, Shoichi; Kawaguchi, Isao; Aoki, Masanari; Kubota, Masahide; Furuhata, Yoshiaki; Shigemura, Yusaku; Yamada, Fumio; Ishikawa, Takahiro; Obara, Satoshi; Yoshida, Satoshi

2015-04-01

The dose rates of radiation absorbed by wild rodents inhabiting a site severely contaminated by the Fukushima Dai-ichi Nuclear Power Plant accident were estimated. The large Japanese field mouse (Apodemus speciosus), also called the wood mouse, was the major rodent species captured in the sampling area, although other species of rodents, such as small field mice (Apodemus argenteus) and Japanese grass voles (Microtus montebelli), were also collected. The external exposure of rodents calculated from the activity concentrations of radiocesium ((134)Cs and (137)Cs) in litter and soil samples using the ERICA (Environmental Risk from Ionizing Contaminants: Assessment and Management) tool under the assumption that radionuclides existed as the infinite plane isotropic source was almost the same as those measured directly with glass dosimeters embedded in rodent abdomens. Our findings suggest that the ERICA tool is useful for estimating external dose rates to small animals inhabiting forest floors; however, the estimated dose rates showed large standard deviations. This could be an indication of the inhomogeneous distribution of radionuclides in the sampled litter and soil. There was a 50-fold difference between minimum and maximum whole-body activity concentrations measured in rodents at the time of capture. The radionuclides retained in rodents after capture decreased exponentially over time. Regression equations indicated that the biological half-life of radiocesium after capture was 3.31 d. At the time of capture, the lowest activity concentration was measured in the lung and was approximately half of the highest concentration measured in the mixture of muscle and bone. The average internal absorbed dose rate was markedly smaller than the average external dose rate (<10% of the total absorbed dose rate). The average total absorbed dose rate to wild rodents inhabiting the sampling area was estimated to be approximately 52 μGy h(-1) (1.2 mGy d(-1)), even 3 years after the accident. This dose rate exceeds 0.1-1 mGy d(-1) derived consideration reference level for Reference rat proposed by the International Commission on Radiological Protection (ICRP). Copyright © 2015 Elsevier Ltd. All rights reserved.

Radiation environment on the Mir orbital station during solar minimum.

PubMed

Badhwar, G D; Atwell, W; Cash, B; Petrov, V M; Akatov YuA; Tchernykh, I V; Shurshakov, V A; Arkhangelsky, V A

1998-01-01

The Mir station has been in a 51.65 degrees inclination orbit since March 1986. In March 1995, the first US astronaut flew on the Mir-18 mission and returned on the Space Shuttle in July 1995. Since then three additional US astronauts have stayed on orbit for up to 6 months. Since the return of the first US astronaut, both the Spektr and Priroda modules have docked with Mir station, altering the mass shielding distribution. Radiation measurements, including the direct comparison of US and Russian absorbed dose rates in the Base Block of the Mir station, were made during the Mir-18 and -19 missions. There is a significant variation of dose rates across the core module; the six locations sampled showed a variation of a factor of nearly two. A tissue equivalent proportional counter (TEPC) measured a total absorbed dose rate of 300 microGy/day, roughly equally divided between the rate due to trapped protons from the South Atlantic Anomaly (SAA) and galactic cosmic radiation (GCR). This dose rate is about a factor of two lower than the rate measured by the thinly shielded (0.5 g cm-2 of Al) operational ion chamber (R-16), and about 3/2 of the rate of the more heavily shielded (3.5 g cm-2 of Al) ion chamber. This is due to the differences in the mass shielding properties at the location of these detectors. A comparison of integral linear energy transfer (LET) spectra measured by TEPC and plastic nuclear track detectors (PNTDs) deployed side by side are in remarkable agreement in the LET region of 15-1000 keV/micrometer, where the PNTDs are fully efficient. The average quality factor, using the ICRP-26 definition, was 2.6, which is higher than normally used. There is excellent agreement between the measured GCR dose rate and model calculations, but this is not true for trapped protons. The measured Mir-18 crew skin dose equivalent rate was 1133 microSv/day. Using the skin dose rate and anatomical models, we have estimated the blood-forming organ (BFO) dose rate and the maximum stay time in orbit for International Space Station crew members.

In vivo urethral dose measurements: a method to verify high dose rate prostate treatments.

PubMed

Brezovich, I A; Duan, J; Pareek, P N; Fiveash, J; Ezekiel, M

2000-10-01

Radiation doses delivered in high dose rate (HDR) brachytherapy are susceptible to many inaccuracies and errors, including imaging, planning and delivery. Consequently, the dose delivered to the patient may deviate substantially from the treatment plan. We investigated the feasibility of using TLD measurements in the urethra to estimate the discrepancy in treatments for prostate cancer. The dose response of the 1 mm diam, 6 mm long LiF rods that we used for the in vivo measurements was calibrated with the 192Ir HDR source, as well as a 60Co teletherapy unit. A train of 20 rods contained in a sterile plastic tube was inserted into the urethral (Foley) catheter for the duration of a treatment fraction, and the measured doses were compared to the treatment plan. Initial results from a total of seven treatments in four patients show good agreement between theory and experiment. Analysis of any one treatment showed agreement within 11.7% +/- 6.2% for the highest dose encountered in the central prostatic urethra, and within 10.4% +/- 4.4% for the mean dose. Taking the average over all seven treatments shows agreement within 1.7% for the maximum urethral dose, and within 1.5% for the mean urethral dose. Based on these initial findings it seems that planned prostate doses can be accurately reproduced in the clinic.

Measuring neutron spectra in radiotherapy using the nested neutron spectrometer.

PubMed

Maglieri, Robert; Licea, Angel; Evans, Michael; Seuntjens, Jan; Kildea, John

2015-11-01

Out-of-field neutron doses resulting from photonuclear interactions in the head of a linear accelerator pose an iatrogenic risk to patients and an occupational risk to personnel during radiotherapy. To quantify neutron production, in-room measurements have traditionally been carried out using Bonner sphere systems (BSS) with activation foils and TLDs. In this work, a recently developed active detector, the nested neutron spectrometer (NNS), was tested in radiotherapy bunkers. The NNS is designed for easy handling and is more practical than the traditional BSS. Operated in current-mode, the problem of pulse pileup due to high dose-rates is overcome by measuring current, similar to an ionization chamber. In a bunker housing a Varian Clinac 21EX, the performance of the NNS was evaluated in terms of reproducibility, linearity, and dose-rate effects. Using a custom maximum-likelihood expectation-maximization algorithm, measured neutron spectra at various locations inside the bunker were then compared to Monte Carlo simulations of an identical setup. In terms of dose, neutron ambient dose equivalents were calculated from the measured spectra and compared to bubble detector neutron dose equivalent measurements. The NNS-measured spectra for neutrons at various locations in a treatment room were found to be consistent with expectations for both relative shape and absolute magnitude. Neutron fluence-rate decreased with distance from the source and the shape of the spectrum changed from a dominant fast neutron peak near the Linac head to a dominant thermal neutron peak in the moderating conditions of the maze. Monte Carlo data and NNS-measured spectra agreed within 30% at all locations except in the maze where the deviation was a maximum of 40%. Neutron ambient dose equivalents calculated from the authors' measured spectra were consistent (one standard deviation) with bubble detector measurements in the treatment room. The NNS may be used to reliably measure the neutron spectrum of a radiotherapy beam in less than 1 h, including setup and data unfolding. This work thus represents a new, fast, and practical method for neutron spectral measurements in radiotherapy.

SU-E-T-113: Dose Distribution Using Respiratory Signals and Machine Parameters During Treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Imae, T; Haga, A; Saotome, N

Purpose: Volumetric modulated arc therapy (VMAT) is a rotational intensity-modulated radiotherapy (IMRT) technique capable of acquiring projection images during treatment. Treatment plans for lung tumors using stereotactic body radiotherapy (SBRT) are calculated with planning computed tomography (CT) images only exhale phase. Purpose of this study is to evaluate dose distribution by reconstructing from only the data such as respiratory signals and machine parameters acquired during treatment. Methods: Phantom and three patients with lung tumor underwent CT scans for treatment planning. They were treated by VMAT while acquiring projection images to derive their respiratory signals and machine parameters including positions ofmore » multi leaf collimators, dose rates and integrated monitor units. The respiratory signals were divided into 4 and 10 phases and machine parameters were correlated with the divided respiratory signals based on the gantry angle. Dose distributions of each respiratory phase were calculated from plans which were reconstructed from the respiratory signals and the machine parameters during treatment. The doses at isocenter, maximum point and the centroid of target were evaluated. Results and Discussion: Dose distributions during treatment were calculated using the machine parameters and the respiratory signals detected from projection images. Maximum dose difference between plan and in treatment distribution was −1.8±0.4% at centroid of target and dose differences of evaluated points between 4 and 10 phases were no significant. Conclusion: The present method successfully evaluated dose distribution using respiratory signals and machine parameters during treatment. This method is feasible to verify the actual dose for moving target.« less

Optimizing drug-dose alerts using commercial software throughout an integrated health care system.

PubMed

Saiyed, Salim M; Greco, Peter J; Fernandes, Glenn; Kaelber, David C

2017-11-01

All default electronic health record and drug reference database vendor drug-dose alerting recommendations (single dose, daily dose, dose frequency, and dose duration) were silently turned on in inpatient, outpatient, and emergency department areas for pediatric-only and nonpediatric-only populations. Drug-dose alerts were evaluated during a 3-month period. Drug-dose alerts fired on 12% of orders (104 098/834 911). System-level and drug-specific strategies to decrease drug-dose alerts were analyzed. System-level strategies included: (1) turning off all minimum drug-dosing alerts, (2) turning off all incomplete information drug-dosing alerts, (3) increasing the maximum single-dose drug-dose alert threshold to 125%, (4) increasing the daily dose maximum drug-dose alert threshold to 125%, and (5) increasing the dose frequency drug-dose alert threshold to more than 2 doses per day above initial threshold. Drug-specific strategies included changing drug-specific maximum single and maximum daily drug-dose alerting parameters for the top 22 drug categories by alert frequency. System-level approaches decreased alerting to 5% (46 988/834 911) and drug-specific approaches decreased alerts to 3% (25 455/834 911). Drug-dose alerts varied between care settings and patient populations. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cardiovascular and hypokalaemic effects of inhaled salbutamol, fenoterol, and isoprenaline.

PubMed Central

Crane, J; Burgess, C; Beasley, R

1989-01-01

The cardiovascular and hypokalaemic effects of equal doses of inhaled fenoterol, isoprenaline and salbutamol were compared in eight healthy male volunteers, in a double blind, placebo controlled study. Increasing doses of 400, 600, and 800 micrograms were given from a metered dose inhaler at 15 minute intervals, followed by measurements of heart rate, blood pressure, total electromechanical systole (as a measure of inotropic response), QTc interval, and plasma potassium concentration. After repeated inhalation, fenoterol resulted in significantly greater chronotropic, electrocardiographic, and hypokalaemic effects than either isoprenaline or salbutamol. The maximum inotropic effect of fenoterol was similar to that of isoprenaline. PMID:2928998

Preliminary Results of Indoor Radon/thoron Concentrations and Terrestrial Gamma Doses in Gejiu, Yunnan, China

NASA Astrophysics Data System (ADS)

Ishikawa, Tetsuo; Tokonami, Shinji; Sun, Quafu; Kobayashi, Yosuke; Min, Xiangdong; Yoshinaga, Shinji

2008-08-01

A preliminary survey on indoor radon/thoron and external gamma ray dose rate was conducted for houses in Gejiu city and its neighboring village in Yunnan Province, China. As a result of the radon/thoron measurements for about 50 houses, very high thoron concentrations were found in some hoses (maximum: 7,900 Bq/m3). The mean annual dose from thoron decay products was estimated to be larger than that from radon decay products (2.9 mSv vs. 1.6 mSv). Further dosimetric and epidemiological studies are needed to investigate the possible effects of radon and thoron.

LET spectra measurements from the STS-35 CPDs

NASA Technical Reports Server (NTRS)

1995-01-01

Linear energy transfer (LET) spectra derived form automated track analysis system (ATAS) track parameter measurements for crew passive dosimeters (CPD's) flown with the astronauts on STS-35 are plotted. The spread between the seven individual spectra is typical of past manual measurements of sets of CPD's. This difference is probably due to the cumulative net shielding variations experienced by the CPD's as the astronauts carrying them went about their activities on the Space Shuttle. The STS-35 mission was launched on Dec. 2, 1990, at 28.5 degrees inclination and 352-km altitude. This is somewhat higher than the nominal 300-km flights and the orbit intersects more of the high intensity trapped proton region in the South Atlantic Anomaly (SAA). However, in comparison with APD spectra measured on earlier lower altitude missions (STS-26, -29, -30, -32), the flux spectra are all roughly comparable. This may be due to the fact that the STS-35 mission took place close to solar maximum (Feb. 1990), or perhaps to shielding differences. The corresponding dose and dose equivalent spectra for this mission are shown. The effect of statistical fluctuations at the higher LET values, where track densities are small, is very noticeable. This results in an increased spread within the dose rate and dose equivalent rate spectra, as compared to the flux spectra. The contribution to dose and dose equivalent per measured track is much greater in the high LET region and the differences, though numerically small, are heavily weighted in the integral spectra. The optimum measurement and characterization of the high LET tails of the spectra represent an important part of the research into plastic nuclear track detector (PNTD) response. The integral flux, dose rate, dose equivalent rate and mission dose equivalent for the seven astronauts are also given.

Degradation of chlorpyrifos residues in apple under temperate conditions of Kashmir Valley.

PubMed

Mukhtar, Malik; Sherwani, Asma; Wani, Ashraf Alam; Ahmed, Sheikh Bilal; Sofi, Javid Ahmad; Bano, Parveena

2015-08-01

The present studies were carried out to observe the dissipation pattern of chlorpyrifos on apple in Kashmir Valley. Persistence of chlorpyrifos in apple was studied following two applications rates of chlorpyrifos (Dursban 20 EC) at 200 g a.i. ha(-1) (single dose T 1) and 400 g a.i. ha(-1) (double dose T 2). The average initial deposit of chlorpyrifos was found to be 1.61 and 1.98 μg g(-1) for T 1 and T 2 application rates respectively on apple. The residues dissipated to 0.09 and 0.06 μg g(-1) after 15- and 30-day post treatment with half-life periods of 3.34 and 5.47 days in T 1 and T 2 application rates, respectively. The residues of chlorpyrifos dissipated to below limit of quantification (LOQ) of 0.04 μg g(-1) after 30 day at T 1 application rate. A waiting period of 6 days must be observed for chlorpyrifos on apple at recommended application rate for the safety of consumers. Theoretical maximum residue contribution (TMRC) values were found to be far less than maximum permissible intake (MPI) at 0 day in both the dosages suggesting chlorpyrifos on apple in Kashmir is unlikely to cause health risks.

Final Technical Report- Radiation Hard Tight Pitch GaInP SPAD Arrays for High Energy Physics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harmon, Eric S.

The specialized photodetectors used in high energy physics experiments often need to remain extremely sensitive for years despite radiation induced damage caused by the constant bombardment of high energy particles. To solve this problem, LightSpin Technologies, Inc. in collaboration with Prof. Bradley Cox and the University of Virginia is developing radiation-hard GaInP photodetectors which are projected to be extraordinarily radiation hard, theoretically capable of withstanding a 100,000-fold higher radiation dose than silicon. In this Phase I SBIR project, LightSpin investigated the performance and radiation hardness of fifth generation GaInP SPAD arrays. These fifth generation devices used a new planar processingmore » approach that enables very tight pitch arrays to be produced. High performance devices with SPAD pitches of 11, 15, and 25 μm were successfully demonstrated, which greatly increased the dynamic range and maximum count rate of the devices. High maximum count rates are critical when considering radiation hardness, since radiation damage causes a proportional increase in the dark count rate, causing SPAD arrays with low maximum count rates (large SPAD pitches) to fail. These GaInP SPAD array Photomultiplier Chips™ were irradiated with protons, electrons, and neutrons. Initial irradiation results were disappointing, with the post-irradiation devices exhibiting excessively high dark currents. The degradation was traced to surface leakage currents that were largely eliminated through the use of trenches etched around the exterior of the Photomultiplier Chip™ (not between SPAD elements). A second round of irradiations on Photomultiplier Chips™ with trenches proved substantially more successful, with post-irradiation dark currents remaining relatively low, though dark count rates were observed to increase at the highest doses. Preliminary analysis of the post-irradiation devices is promising … many of the irradiated Photomultiplier Chips™ still exhibit good gain characteristics after 1E12/cm 2 – 1E13/cm 2 doses and have apparent dark count rates that are lower than the apparent dark count rates published for irradiation of silicon SPAD arrays (silicon photomultipliers or SiPMs). Some post-irradiation results are still pending because the samples will still too radioactive to be shipped back from the irradiation facility for post-irradiation testing.« less

A step-up test procedure to find the minimum effective dose.

PubMed

Wang, Weizhen; Peng, Jianan

2015-01-01

It is of great interest to find the minimum effective dose (MED) in dose-response studies. A sequence of decreasing null hypotheses to find the MED is formulated under the assumption of nondecreasing dose response means. A step-up multiple test procedure that controls the familywise error rate (FWER) is constructed based on the maximum likelihood estimators for the monotone normal means. When the MED is equal to one, the proposed test is uniformly more powerful than Hsu and Berger's test (1999). Also, a simulation study shows a substantial power improvement for the proposed test over four competitors. Three R-codes are provided in Supplemental Materials for this article. Go to the publishers online edition of Journal of Biopharmaceutical Statistics to view the files.

Moving Beyond Maximum Tolerated Dose for Targeted Oncology Drugs: Use of Clinical Utility Index to Optimize Venetoclax Dosage in Multiple Myeloma Patients.

PubMed

Freise, K J; Jones, A K; Verdugo, M E; Menon, R M; Maciag, P C; Salem, A H

2017-12-01

Exposure-response analyses of venetoclax in combination with bortezomib and dexamethasone in previously treated patients with multiple myeloma (MM) were performed on a phase Ib venetoclax dose-ranging study. Logistic regression models were utilized to determine relationships, identify subpopulations with different responses, and optimize the venetoclax dosage that balanced both efficacy and safety. Bortezomib refractory status and number of prior treatments were identified to impact the efficacy response to venetoclax treatment. Higher venetoclax exposures were estimated to increase the probability of achieving a very good partial response (VGPR) or better through venetoclax doses of 1,200 mg. However, the probability of neutropenia (grade ≥3) was estimated to increase at doses >800 mg. Using a clinical utility index, a venetoclax dosage of 800 mg daily was selected to optimally balance the VGPR or better rates and neutropenia rates in MM patients administered 1-3 prior lines of therapy and nonrefractory to bortezomib. © 2017 American Society for Clinical Pharmacology and Therapeutics.

[Estimation of Maximum Entrance Skin Dose during Cerebral Angiography].

PubMed

Kawauchi, Satoru; Moritake, Takashi; Hayakawa, Mikito; Hamada, Yusuke; Sakuma, Hideyuki; Yoda, Shogo; Satoh, Masayuki; Sun, Lue; Koguchi, Yasuhiro; Akahane, Keiichi; Chida, Koichi; Matsumaru, Yuji

2015-09-01

Using radio-photoluminescence glass dosimeter, we measured the entrance skin dose (ESD) in 46 cases and analyzed the correlations between maximum ESD and angiographic parameters [total fluoroscopic time (TFT); number of digital subtraction angiography (DSA) frames, air kerma at the interventional reference point (AK), and dose-area product (DAP)] to estimate the maximum ESD in real time. Mean (± standard deviation) maximum ESD, dose of the right lens, and dose of the left lens were 431.2 ± 135.8 mGy, 33.6 ± 15.5 mGy, and 58.5 ± 35.0 mGy, respectively. Correlation coefficients (r) between maximum ESD and TFT, number of DSA frames, AK, and DAP were r=0.379 (P<0.01), r=0.702 (P<0.001), r=0.825 (P<0.001), and r=0.709 (P<0.001), respectively. AK was identified as the most useful parameter for real-time prediction of maximum ESD. This study should contribute to the development of new diagnostic reference levels in our country.

Measurements of the neutron spectrum on the Martian surface with MSL/RAD

NASA Astrophysics Data System (ADS)

Köhler, J.; Zeitlin, C.; Ehresmann, B.; Wimmer-Schweingruber, R. F.; Hassler, D. M.; Reitz, G.; Brinza, D. E.; Weigle, G.; Appel, J.; Böttcher, S.; Böhm, E.; Burmeister, S.; Guo, J.; Martin, C.; Posner, A.; Rafkin, S.; Kortmann, O.

2014-03-01

The Radiation Assessment Detector (RAD), onboard the Mars Science Laboratory (MSL) rover Curiosity, measures the energetic charged and neutral particles and the radiation dose rate on the surface of Mars. An important factor for determining the biological impact of the Martian surface radiation is the specific contribution of neutrons, with their deeper penetration depth and ensuing high biological effectiveness. This is very difficult to measure quantitatively, resulting in considerable uncertainties in the total radiation dose. In contrast to charged particles, neutral particles (neutrons and gamma rays) are generally only measured indirectly. Measured spectra are a complex convolution of the incident particle spectrum with the detector response function and must be unfolded. We apply an inversion method (based on a maximum likelihood estimation) to calculate the neutron and gamma spectra from the RAD neutral particle measurements. Here we show the first spectra on the surface of Mars and compare them to theoretical predictions. The measured neutron spectrum (ranging from 8 to 740 MeV) translates into a radiation dose rate of 14±4μGy/d and a dose equivalent rate of 61±15μSv/d. This corresponds to 7% of the measured total surface dose rate and 10% of the biologically relevant surface dose equivalent rate on Mars. Measuring the Martian neutron and gamma spectra is an essential step for determining the mutagenic influences to past or present life at or beneath the Martian surface as well as the radiation hazard for future human exploration, including the shielding design of a potential habitat.

Stereotactic Body Radiation Therapy Boost After Concurrent Chemoradiation for Locally Advanced Non-Small Cell Lung Cancer: A Phase 1 Dose Escalation Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hepel, Jaroslaw T., E-mail: jhepel@lifespan.org; Department of Radiation Oncology, Tufts Medical Center, Tufts University, Boston, Massachusetts; Leonard, Kara Lynne

Purpose: Stereotactic body radiation therapy (SBRT) boost to primary and nodal disease after chemoradiation has potential to improve outcomes for advanced non-small cell lung cancer (NSCLC). A dose escalation study was initiated to evaluate the maximum tolerated dose (MTD). Methods and Materials: Eligible patients received chemoradiation to a dose of 50.4 Gy in 28 fractions and had primary and nodal volumes appropriate for SBRT boost (<120 cc and <60 cc, respectively). SBRT was delivered in 2 fractions after chemoradiation. Dose was escalated from 16 to 28 Gy in 2 Gy/fraction increments, resulting in 4 dose cohorts. MTD was defined when ≥2 of 6 patients permore » cohort experienced any treatment-related grade 3 to 5 toxicity within 4 weeks of treatment or the maximum dose was reached. Late toxicity, disease control, and survival were also evaluated. Results: Twelve patients (3 per dose level) underwent treatment. All treatment plans met predetermined dose-volume constraints. The mean age was 64 years. Most patients had stage III disease (92%) and were medically inoperable (92%). The maximum dose level was reached with no grade 3 to 5 acute toxicities. At a median follow-up time of 16 months, 1-year local-regional control (LRC) was 78%. LRC was 50% at <24 Gy and 100% at ≥24 Gy (P=.02). Overall survival at 1 year was 67%. Late toxicity (grade 3-5) was seen in only 1 patient who experienced fatal bronchopulmonary hemorrhage (grade 5). There were no predetermined dose constraints for the proximal bronchial-vascular tree (PBV) in this study. This patient's 4-cc PBV dose was substantially higher than that received by other patients in all 4 cohorts and was associated with the toxicity observed: 20.3 Gy (P<.05) and 73.5 Gy (P=.07) for SBRT boost and total treatment, respectively. Conclusions: SBRT boost to both primary and nodal disease after chemoradiation is feasible and well tolerated. Local control rates are encouraging, especially at doses ≥24 Gy in 2 fractions. Toxicity at the PBV is a concern but potentially can be avoided with strict dose-volume constraints.« less

Phase 1 Dose Escalation Study of Accelerated Radiation Therapy With Concurrent Chemotherapy for Locally Advanced Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kelsey, Chris R., E-mail: christopher.kelsey@duke.edu; Das, Shiva; Gu, Lin

2015-12-01

Purpose: To determine the maximum tolerated dose of radiation therapy (RT) given in an accelerated fashion with concurrent chemotherapy using intensity modulated RT. Methods and Materials: Patients with locally advanced lung cancer (non-small cell and small cell) with good performance status and minimal weight loss received concurrent cisplatin and etoposide with RT. Intensity modulated RT with daily image guidance was used to facilitate esophageal avoidance and delivered using 6 fractions per week (twice daily on Fridays with a 6-hour interval). The dose was escalated from 58 Gy to a planned maximum dose of 74 Gy in 4 Gy increments in a standardmore » 3 + 3 trial design. Dose-limiting toxicity (DLT) was defined as acute grade 3-5 nonhematologic toxicity attributed to RT. Results: A total of 24 patients were enrolled, filling all dose cohorts, all completing RT and chemotherapy as prescribed. Dose-limiting toxicity occurred in 1 patient at 58 Gy (grade 3 esophagitis) and 1 patient at 70 Gy (grade 3 esophageal fistula). Both patients with DLTs had large tumors (12 cm and 10 cm, respectively) adjacent to the esophagus. Three additional patients were enrolled at both dose cohorts without further DLT. In the final 74-Gy cohort, no DLTs were observed (0 of 6). Conclusions: Dose escalation and acceleration to 74 Gy with intensity modulated RT and concurrent chemotherapy was tolerable, with a low rate of grade ≥3 acute esophageal reactions.« less

Droplet Characterization and Penetration of an Ultra-Low Volume Mosquito Adulticide Spray Targeting the Asian Tiger Mosquito, Aedes albopictus, within Urban and Suburban Environments of Northeastern USA

PubMed Central

Faraji, Ary; Unlu, Isik; Crepeau, Taryn; Healy, Sean; Crans, Scott; Lizarraga, Griffith; Fonseca, Dina; Gaugler, Randy

2016-01-01

Adult control of Aedes albopictus via ultra-low volume is difficult because this species occurs primarily in peridomestic habitats where obstacles such as buildings and vegetation can disrupt spray plumes and droplet dispersion. We determined droplet penetration and characterization of a pyrethroid adulticide applied from the ground at mid (46.77 ml/ha) and maximum (93.53 ml/ha) label rates within cryptic habitats of urban and suburban environments. Droplets were collected from all habitats, with no significant differences detected between locations within the same application rate or collection method. No differences were detected in droplet densities (drops per mm2) between rates within urban environments, but more droplets were collected in urban (149.93 ± 11.07 SE) than suburban sites (114.37 ± 11.32) at the maximum label rate (P = 0.003). The excellent penetration of aerosols into cryptic habitats of an urban site was likely due to the shorter spray paths afforded by our network of roads and alleys. Mid label rates displayed similar droplet density values as maximum label rates in urban areas, indicating that lower rates may be used effectively to reduce costs, lessen non-target effects, and increase environmental stewardship. Advances in formulations and technology are driving changes in adulticide applications, leading to use of the minimum effective dose for maximum efficacy, precision, and accountability. PMID:27116103

Single-dose infusion of sodium butyrate, but not lactose, increases plasma ß-hydroxybutyrate and insulin in lactating dairy cows

USDA-ARS?s Scientific Manuscript database

Several previous studies have identified beneficial effects of butyrate on rumen development and intestinal health in pre-ruminants. These encouraging findings have led to further investigations related to butyrate supplementation in the mature ruminant. However, the maximum tolerable dosage rate of...

Method for the prediction of the effective dose equivalent to the crew of the International Space Station

NASA Astrophysics Data System (ADS)

El-Jaby, Samy; Tomi, Leena; Sihver, Lembit; Sato, Tatsuhiko; Richardson, Richard B.; Lewis, Brent J.

2014-03-01

This paper describes a methodology for assessing the pre-mission exposure of space crew aboard the International Space Station (ISS) in terms of an effective dose equivalent. In this approach, the PHITS Monte Carlo code was used to assess the particle transport of galactic cosmic radiation (GCR) and trapped radiation for solar maximum and minimum conditions through an aluminum shield thickness. From these predicted spectra, and using fluence-to-dose conversion factors, a scaling ratio of the effective dose equivalent rate to the ICRU ambient dose equivalent rate at a 10 mm depth was determined. Only contributions from secondary neutrons, protons, and alpha particles were considered in this analysis. Measurements made with a tissue equivalent proportional counter (TEPC) located at Service Module panel 327, as captured through a semi-empirical correlation in the ISSCREM code, where then scaled using this conversion factor for prediction of the effective dose equivalent. This analysis shows that at this location within the service module, the total effective dose equivalent is 10-30% less than the total TEPC dose equivalent. Approximately 75-85% of the effective dose equivalent is derived from the GCR. This methodology provides an opportunity for pre-flight predictions of the effective dose equivalent and therefore offers a means to assess the health risks of radiation exposure on ISS flight crew.

Gamma-ray exposure hazard due to stowage of M-774 APFSDS (Armour-piercing fin-stabilized discarding-sabot) rounds in a Leopard C-1 main battle tank. Technical note

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robitaille, H.A.

1983-09-01

The M-744 APFSDS anti-tank round contains a depleted-uranium penetrator of 3.4 kgram mass. Since depleted uranium is naturally radioactive, the storage of a substantial number of these rounds inside a Leopard C-1 main battle tank creates a gamma radiation field within the vehicle. Gamma-ray exposure rates have been measured using a sodium-iodide spectrometer at each of the four crew-member locations and for two turret orientations, with 59 rounds stowed in the vehicle. In all cases the measured gamma-ray dose rates were less than a maximum of 0.17 millirad per hour observed at the loader's position. Assuming the loader spent anmore » entire week (168 hours) at his station, his integrated dose would amount to 29 mRad - approximately a factor of 4 lower than the maximum currently allowed by Canadian Forces regulations. It is therefore concluded that the M774 round does not represent a significant gamma radiation hazard to Leopard C1 crewmembers.« less

Environmental dose rate distribution along the Romanian Black Sea shore

NASA Astrophysics Data System (ADS)

Duliu, Octavian G.; Margineanu, Romul M.; Blebea-Apostu, Ana-Maria; Gomoiu, Claudia; Bercea, Sorin

2013-04-01

The radiometric investigation of the natural radioactivity dose rate distribution along the most important Romanian Black Sea tourist resorts showed values between 34 and 54 nSv/h, lower than the 59 nSv/h, the average background reported for the entire Romanian territory. At the same time we have noticed that the experimental dose rates monotonously increase northward, reaching a maximum in the vicinity of Vadu and Corbu beaches, both on the southern part of the Chituc sandbank. Concurrent gamma ray spectrometric measurements, performed at the Slanic-Prahova Low-Background Radiation Laboratory for sand samples collected from the same location, have shown that the natural radionuclides have a major contribution to background radiation while anthropogenic Cs-137 plays, 26 years after Chernobyl catastrophe, a negligible role. The experimental values of activity concentrations of all radionuclides present in sand samples were used to calculate the corresponding values of dose rates to which, by adding the contribution of cosmic rays, we have obtained values coincident, within experimental uncertainties, with the experimental ones. At the same time, on Chituc sandbank, a transverse profile of dose rate distribution revealed the presence of some local maxima, two to thee times higher then the average ones. Subsequent gamma ray spectrometry showed an increased content of natural radionuclides, most probably due to a local accumulation of heavy minerals, a common occurrence in the vicinity of river deltas, in our case the Danube Delta. In such a way, the monitoring of local dose rate distribution could be very useful not only in attesting the environmental quality of various resorts and beaches, but also, in signaling the presence of heavy minerals, with beneficent economic consequences.

Relative bioavailability and plasma paracetamol profiles of Panadol suppositories in children.

PubMed

Coulthard, K P; Nielson, H W; Schroder, M; Covino, A; Matthews, N T; Murray, R S; Van Der Walt, J H

1998-10-01

To determine the relative bioavailability and plasma paracetamol concentration profiles following administration of a proprietary formulation of paracetamol suppositories to postoperative children. Study A-eight children undergoing minor surgery had blood samples collected following the rectal administration of either a 250 mg or 500 mg paracetamol suppository on one day and an equivalent oral dose on the following day. A mean dose of 13 mg/kg gave a mean Cmax (Tmax) of 7.7 mg/L (1.6 h) and 4.9 mg/L (2.0 h) following oral and rectal administration, respectively. The mean relative rectal bioavailability was 78% (95% confidence interval of 55-101%). Study B-20 children undergoing tonsillectomy and/or adenoidectomy were randomly assigned to receive a postoperative dose of 500 mg of paracetamol either as 2 x 250 mg liquid filled or 1 x 500 mg hard wax Panadol suppository. A mean dose of 25 mg/kg produced mean maximum plasma paracetamol concentrations of 13.2 mg/L and 14.5 mg/L at 2.1 and 1.9 h for the hard and liquid filled suppository, respectively. The absorption rate constants and areas under the curves suggested no difference in the rate or extent of absorption between the two formulations. Absorption of paracetamol following rectal administration of Panadol suppositories to postoperative children is slower and reduced as compared to oral therapy. The hard wax and liquid filled products have similar absorption characteristics. The usually quoted antipyretic therapeutic range for paracetamol is 10-20 mg/L, although 5 mg/L may be effective. A single rectal dose of 25 mg/kg will obtain this lower concentration within 1 h of administration and maintain it for up to 6 h. When given in an appropriate dose for analgesia, maximum plasma paracetamol concentrations would be available in the immediate postoperative period if the rectal dose was given 2 h before the planned end of the procedure.

WE-AB-209-10: Optimizing the Delivery of Sequential Fluence Maps for Efficient VMAT Delivery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Craft, D; Balvert, M

2016-06-15

Purpose: To develop an optimization model and solution approach for computing MLC leaf trajectories and dose rates for high quality matching of a set of optimized fluence maps to be delivered sequentially around a patient in a VMAT treatment. Methods: We formulate the fluence map matching problem as a nonlinear optimization problem where time is discretized but dose rates and leaf positions are continuous variables. For a given allotted time, which is allocated across the fluence maps based on the complexity of each fluence map, the optimization problem searches for the best leaf trajectories and dose rates such that themore » original fluence maps are closely recreated. Constraints include maximum leaf speed, maximum dose rate, and leaf collision avoidance, as well as the constraint that the ending leaf positions for one map are the starting leaf positions for the next map. The resulting model is non-convex but smooth, and therefore we solve it by local searches from a variety of starting positions. We improve solution time by a custom decomposition approach which allows us to decouple the rows of the fluence maps and solve each leaf pair individually. This decomposition also makes the problem easily parallelized. Results: We demonstrate method on a prostate case and a head-and-neck case and show that one can recreate fluence maps to high degree of fidelity in modest total delivery time (minutes). Conclusion: We present a VMAT sequencing method that reproduces optimal fluence maps by searching over a vast number of possible leaf trajectories. By varying the total allotted time given, this approach is the first of its kind to allow users to produce VMAT solutions that span the range of wide-field coarse VMAT deliveries to narrow-field high-MU sliding window-like approaches.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, H; Lin, H; Darafsheh, A

Purpose: To characterize basic performance of plastic scintillator detectors (PSD) designed for dosimetry of radiation therapy. Methods: The Exradin W1 Scintillator is a plastic scintillating fiber-based detector designed for highly accurate measurement of small radiotherapy fields used in patient plan verification and machine commissioning and QA procedures. The Cerenkov emissions were corrected using spectral separation. The optical signal was converted to electronic signal with a photodiode. We measured its dosimetry performance, including percentage depth dose, output factor, dose and dose rate linear response. We compared the dosimetry results with reference ion chamber measurements. Results: The dosimetry results of PSD agreemore » well with reference ion chamber measurements. For percentage depth dose, the differences between PSD and ion chamber results are on average 1.7±1.1% and 0.8±0.8% with a maximum of 3.5% and 2.7% for 6MV and 15MV beams, respectively. For the output factors, PSD measurements are within 2% from ion chamber results. The dose linear response is within 1% when dose is larger than 20 MU for both 6 MV and 15 MV. The dose rate linear response is within 1% for the entire dose rate used (100 MU/min to 600MU/min). Conclusions: The current design of PSD is feasible for the dosimtry measurement in radiation therapy. This combination of PSD and photodiode system could be extended to multichannel array detection of dose distribution. It might as well be used as range verification in proton therapy. The work is partially supported by: DOD (W81XWH-09-2-0174) and American Cancer Society (IRG-78-002-28)« less

High dose psilocybin is associated with positive subjective effects in healthy volunteers.

PubMed

Nicholas, Christopher R; Henriquez, Kelsey M; Gassman, Michele C; Cooper, Karen M; Muller, Daniel; Hetzel, Scott; Brown, Randall T; Cozzi, Nicholas V; Thomas, Chantelle; Hutson, Paul R

2018-06-01

The aim of the current study was to investigate the relationship between escalating higher doses of psilocybin and the potential psilocybin occasioned positive subjective effects. Healthy participants ( n=12) were given three escalating doses of oral psilocybin (0.3 mg/kg; 0.45 mg/kg; 0.6 mg/kg) or (18.8-36.6 mg; 27.1-54.0 mg; 36.3-59.2 mg) a minimum of four weeks apart in a supervised setting. Blood and urine samples, vital signs, and electrocardiograms were obtained. Subjective effects were assessed using the Mystical Experience Questionnaire and Persisting Effects Questionnaire. There was a significant linear dose-related response in Mystical Experience Questionnaire total score and the transcendence of time and space subscale, but not in the rate of a complete mystical experience. There was also a significant difference between dose 3 compared to dose 1 on the transcendence of time and space subscale, while no dose-related differences were found for Mystical Experience Questionnaire total scores or rate of a mystical experience. Persisting Effects Questionnaire positive composite scores 30 days after completion of the last dose were significantly higher than negative composite scores. Persisting Effects Questionnaire results revealed a moderate increase in sense of well-being or life satisfaction on average that was associated with the maximum Mystical Experience Questionnaire total score. Pharmacokinetic measures were associated with dose but not with Mystical Experience Questionnaire total scores or rate of a mystical experience. High doses of psilocybin elicited subjective effects at least as strong as the lower doses and resulted in positive persisting subjective effects 30 days after, indicating that a complete mystical experience was not a prerequisite for positive outcomes.

Technical Note: A proposal of air ventilation system design criteria for a clinical room in a heavy-ion medical facility.

PubMed

Kum, Oyeon

2018-06-01

An optimized air ventilation system design for a treatment room in Heavy-ion Medical Facility is an important issue in the aspects of nuclear safety because the activated air produced in a treatment room can directly affect the medical staff and the general public in the radiation-free area. Optimized design criteria of air ventilation system for a clinical room in 430 MeV/u carbon ion beam medical accelerator facility was performed by using a combination of MCNPX2.7.0 and CINDER'90 codes. Effective dose rate and its accumulated effective dose by inhalation and residual gamma were calculated for a normal treatment scenario (2 min irradiation for one fraction) as a function of decay time. Natural doses around the site were measured before construction and used as reference data. With no air ventilation system, the maximum effective dose rate was about 3 μSv/h (total dose of 90 mSv/y) and minimum 0.2 μSv/h (total dose of 6 mSv/y), which are over the legal limits for medical staff and for the general public. Although inhalation dose contribution was relatively small, it was considered seriously because of its long-lasting effects in the body. The integrated dose per year was 1.8 mSv/y in the radiation-free area with the 20-min rate of air ventilation system. An optimal air ventilation rate of 20 min is proposed for a clinical room, which also agrees with the best mechanical design value. © 2018 American Association of Physicists in Medicine.

Radiation Pneumopathy in the Rat After Intravenous Application of {sup 188}Re-Labeled Microspheres

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liepe, Knut; Faulhaber, Diana; Wunderlich, Gerd

2011-10-01

Purpose: To determine the dose dependence and kinetics of pneumopathy after systemic administration of rhenium-188 ({sup 188}Re)-labeled microspheres in a rat model. Methods and Materials: {sup 188}Re-microspheres were injected intravenously into adult Wistar rats (n = 54, age, 8 {+-} 2 months). The rats were divided into 6 groups according to the intended absorbed dose in the lung (maximum 60 Gy). Gamma camera scans were used to estimate the individual whole lung doses. One control group (n = 5) received nonlabeled microspheres. The breathing rate was measured before and weekly after the treatment using whole body plethysmography until 24 weeks.more » An increase in the breathing rate by 20% compared with the individual pretreatment control value was defined as the quantal endpoint for dose-effect analyses. Results: A biphasic increase in the breathing rate was observed. The first impairment of lung function occurred in Weeks 3-6. For late changes, the interval to onset was clearly dose dependent and was 17 weeks (10-30 Gy) and 10 weeks (50-60 Gy), respectively. The incidence of the response was highly dependent on the estimated lung dose. The median effective dose for an early and late response was virtually identical (19.9 {+-} 0.6 Gy and 20.4 {+-} 3.1 Gy, respectively). A significant correlation was found between the occurrence of an early and a late effect in the same rat, suggesting a strong consequential component. Conclusions: The effects of radiolabeled microspheres can be studied longitudinally in a rat model, using changes in the breathing rate as the functional, clinically relevant response. The isoeffective doses from the present study using radionuclide administration and those from published investigations of homogeneous external beam radiotherapy are almost similar.« less

Measurements of the neutron spectrum in transit to Mars on the Mars Science Laboratory.

PubMed

Köhler, J; Ehresmann, B; Zeitlin, C; Wimmer-Schweingruber, R F; Hassler, D M; Reitz, G; Brinza, D E; Appel, J; Böttcher, S; Böhm, E; Burmeister, S; Guo, J; Lohf, H; Martin, C; Posner, A; Rafkin, S

2015-04-01

The Mars Science Laboratory spacecraft, containing the Curiosity rover, was launched to Mars on 26 November 2011. Although designed for measuring the radiation on the surface of Mars, the Radiation Assessment Detector (RAD) measured the radiation environment inside the spacecraft during most of the 253-day, 560-million-kilometer cruise to Mars. An important factor for determining the biological impact of the radiation environment inside the spacecraft is the specific contribution of neutrons with their high biological effectiveness. We apply an inversion method (based on a maximum-likelihood estimation) to calculate the neutron and gamma spectra from the RAD neutral particle measurements. The measured neutron spectrum (12-436 MeV) translates into a radiation dose rate of 3.8±1.2 μGy/day and a dose equivalent of 19±5 μSv/day. Extrapolating the measured spectrum (0.1-1000 MeV), we find that the total neutron-induced dose rate is 6±2 μGy/day and the dose equivalent rate is 30±10 μSv/day. For a 360 day round-trip from Earth to Mars with comparable shielding, this translates into a neutron induced dose equivalent of about 11±4 mSv. Copyright © 2015 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

Outcomes of Direct Vision Internal Urethrotomy for Bulbar Urethral Strictures: Technique Modification with High Dose Triamcinolone Injection.

PubMed

Modh, Rishi; Cai, Peter Y; Sheffield, Alyssa; Yeung, Lawrence L

2015-01-01

Objective. To evaluate the recurrence rate of bulbar urethral strictures managed with cold knife direct vision internal urethrotomy and high dose corticosteroid injection. Methods. 28 patients with bulbar urethral strictures underwent direct vision internal urethrotomy with high dose triamcinolone injection into the periurethral tissue and were followed up for recurrence. Results. Our cohort had a mean age of 60 years and average stricture length of 1.85 cm, and 71% underwent multiple previous urethral stricture procedures with an average of 5.7 procedures each. Our technique modification of high dose corticosteroid injection had a recurrence rate of 29% at a mean follow-up of 20 months with a low rate of urinary tract infections. In patients who failed treatment, mean time to stricture recurrence was 7 months. Patients who were successfully treated had significantly better International Prostate Symptom Scores at 6, 9, and 12 months. There was no significant difference in maximum flow velocity on Uroflowmetry at last follow-up but there was significant difference in length of follow-up (p = 0.02). Conclusions. High dose corticosteroid injection at the time of direct vision internal urethrotomy is a safe and effective procedure to delay anatomical and symptomatic recurrence of bulbar urethral strictures, particularly in those who are poor candidates for urethroplasty.

Chemical carcinogenesis: Too many rodent carcinogens

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ames, B.N.; Gold, L.S.

1990-10-01

The administration of chemicals at the maximum tolerated dose (MTD) in standard animal cancer tests is postulated to increase cell division (mitogenesis), which in turn increases rates of mutagenesis and thus carcinogenesis. The animal data are consistent with this mechanism, because a high proportion{endash}about half{endash}of all chemicals tested (whether natural or synthetic) are indeed rodent carcinogens. The authors conclude that at the low doses of most human exposures, where cell killing does not occur, the hazards to humans of rodent carcinogens may be much lower than is commonly assumed.

Reinvestigation of the relationship between the amplitude of the first heart sound to cardiac dynamics.

PubMed

Tang, Hong; Ruan, Chengjie; Qiu, Tianshuang; Park, Yongwan; Xiao, Shouzhong

2013-08-01

The relationships between the amplitude of the first heart sound (S1) and the rising rate of left ventricular pressure (LVP) concluded in previous studies were not consistent. Some researchers believed the relationship was positively linear; others stated the relationship was only positively correlated. To further investigate this relationship, this study simultaneously sampled the external phonocardiogram, electrocardiogram, and intracardiac pressure in the left ventricle in three anesthetized dogs, while invoking wide hemodynamic changes using various doses of epinephrine. The relationship between the maximum amplitude of S1 and the maximum rising rate of LVP and the relationship between the amplitude of dominant peaks/valleys and the corresponding rising rate of LVP were examined by linear, quadratic, cubic, and exponential models. The results showed that the relationships are best fit by nonlinear exponential models.

High dose rates obtained outside ISS in June 2015 during SEP event.

PubMed

Dachev, T P; Tomov, B T; Matviichuk, Yu N; Dimitrov, Pl G; Bankov, N G

2016-06-01

The R3DR2 instrument performed measurements in the European Space Agency (ESA) EXPOSE-R2 platform outside the Russian "Zvezda" module of the International Space Station (ISS) in the period 24 October 2014-11 January 2016. It is the Liulin-type deposited energy spectrometer (DES) (Dachev et al., 2015a). Took place in November 2014, this was the first attempt to monitor a small solar energetic particle (SEP) event outside ISS using the Liulin-type DES (Dachev et al., 2015d). In this study, we describe the dosimetric characteristics of the largest SEP event, observed on 22 June 2015 with the R3DR2 instrument outside ISS. The main finding of this study is that SEP protons with a minimum energy of approximately 7MeV at the surface of the R3DR2 detector produced high dose rates, reaching >5000µGyh(-1), while the inner radiation belt maximum dose was at the level of 2200µGyh(-1). If a virtual external vehicle activity (EVA) was performed in the same period of the SEP maximum on 22 June 2015, the doses obtained in the skin of cosmonauts/astronauts can reach 2.84mGy after 6.5h, which is similar to the average absorbed dose inside ISS for 15days (Reitz et al., 2005). A comparison with other extreme events measured with Liulin-type instruments shows that SEPs similar to that observed on 22 June 2015 could be one of the most dangerous events for the cosmonauts/astronauts involved in EVA. Copyright © 2016 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

A new approach using coagulation rate constant for evaluation of turbidity removal

NASA Astrophysics Data System (ADS)

Al-Sameraiy, Mukheled

2017-06-01

Coagulation-flocculation-sedimentation processes for treating three levels of bentonite synthetic turbid water using date seeds (DS) and alum (A) coagulants were investigated in the previous research work. In the current research, the same experimental results were used to adopt a new approach on a basis of using coagulation rate constant as an investigating parameter to identify optimum doses of these coagulants. Moreover, the performance of these coagulants to meet (WHO) turbidity standard was assessed by introducing a new evaluating criterion in terms of critical coagulation rate constant (kc). Coagulation rate constants (k2) were mathematically calculated in second order form of coagulation process for each coagulant. The maximum (k2) values corresponded to doses, which were obviously to be considered as optimum doses. The proposed criterion to assess the performance of coagulation process of these coagulants was based on the mathematical representation of (WHO) turbidity guidelines in second order form of coagulation process stated that (k2) for each coagulant should be ≥ (kc) for each level of synthetic turbid water. For all tested turbid water, DS coagulant could not satisfy it. While, A coagulant could satisfy it. The results obtained in the present research are exactly in agreement with the previous published results in terms of finding optimum doses for each coagulant and assessing their performances. On the whole, it is recommended considering coagulation rate constant to be a new approach as an indicator for investigating optimum doses and critical coagulation rate constant to be a new evaluating criterion to assess coagulants' performance.

Assessment of radiation shield integrity of DD/DT fusion neutron generator facilities by Monte Carlo and experimental methods

NASA Astrophysics Data System (ADS)

Srinivasan, P.; Priya, S.; Patel, Tarun; Gopalakrishnan, R. K.; Sharma, D. N.

2015-01-01

DD/DT fusion neutron generators are used as sources of 2.5 MeV/14.1 MeV neutrons in experimental laboratories for various applications. Detailed knowledge of the radiation dose rates around the neutron generators are essential for ensuring radiological protection of the personnel involved with the operation. This work describes the experimental and Monte Carlo studies carried out in the Purnima Neutron Generator facility of the Bhabha Atomic Research Center (BARC), Mumbai. Verification and validation of the shielding adequacy was carried out by measuring the neutron and gamma dose-rates at various locations inside and outside the neutron generator hall during different operational conditions both for 2.5-MeV and 14.1-MeV neutrons and comparing with theoretical simulations. The calculated and experimental dose rates were found to agree with a maximum deviation of 20% at certain locations. This study has served in benchmarking the Monte Carlo simulation methods adopted for shield design of such facilities. This has also helped in augmenting the existing shield thickness to reduce the neutron and associated gamma dose rates for radiological protection of personnel during operation of the generators at higher source neutron yields up to 1 × 1010 n/s.

SU-F-T-18: The Importance of Immobilization Devices in Brachytherapy Treatments of Vaginal Cuff

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shojaei, M; Dumitru, N; Pella, S

2016-06-15

Purpose: High dose rate brachytherapy is a highly localized radiation therapy that has a very high dose gradient. Thus one of the most important parts of the treatment is the immobilization. The smallest movement of the patient or applicator can result in dose variation to the surrounding tissues as well as to the tumor to be treated. We will revise the ML Cylinder treatments and their localization challenges. Methods: A retrospective study of 25 patients with 5 treatments each looking into the applicator’s placement in regard to the organs at risk. Motion possibilities for each applicator intra and inter fractionationmore » with their dosimetric implications were covered and measured in regard with their dose variance. The localization immobilization devices used were assessed for the capability to prevent motion before and during the treatment delivery. Results: We focused on the 100% isodose on central axis and a 15 degree displacement due to possible rotation analyzing the dose variations to the bladder and rectum walls. The average dose variation for bladder was 15% of the accepted tolerance, with a minimum variance of 11.1% and a maximum one of 23.14% on the central axis. For the off axis measurements we found an average variation of 16.84% of the accepted tolerance, with a minimum variance of 11.47% and a maximum one of 27.69%. For the rectum we focused on the rectum wall closest to the 120% isodose line. The average dose variation was 19.4%, minimum 11.3% and a maximum of 34.02% from the accepted tolerance values Conclusion: Improved immobilization devices are recommended. For inter-fractionation, localization devices are recommended in place with consistent planning in regards with the initial fraction. Many of the present immobilization devices produced for external radiotherapy can be used to improve the localization of HDR applicators during transportation of the patient and during treatment.« less

Predicting Nonauditory Adverse Radiation Effects Following Radiosurgery for Vestibular Schwannoma: A Volume and Dosimetric Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hayhurst, Caroline; Monsalves, Eric; Bernstein, Mark

2012-04-01

Purpose: To define clinical and dosimetric predictors of nonauditory adverse radiation effects after radiosurgery for vestibular schwannoma treated with a 12 Gy prescription dose. Methods: We retrospectively reviewed our experience of vestibular schwannoma patients treated between September 2005 and December 2009. Two hundred patients were treated at a 12 Gy prescription dose; 80 had complete clinical and radiological follow-up for at least 24 months (median, 28.5 months). All treatment plans were reviewed for target volume and dosimetry characteristics; gradient index; homogeneity index, defined as the maximum dose in the treatment volume divided by the prescription dose; conformity index; brainstem; andmore » trigeminal nerve dose. All adverse radiation effects (ARE) were recorded. Because the intent of our study was to focus on the nonauditory adverse effects, hearing outcome was not evaluated in this study. Results: Twenty-seven (33.8%) patients developed ARE, 5 (6%) developed hydrocephalus, 10 (12.5%) reported new ataxia, 17 (21%) developed trigeminal dysfunction, 3 (3.75%) had facial weakness, and 1 patient developed hemifacial spasm. The development of edema within the pons was significantly associated with ARE (p = 0.001). On multivariate analysis, only target volume is a significant predictor of ARE (p = 0.001). There is a target volume threshold of 5 cm3, above which ARE are more likely. The treatment plan dosimetric characteristics are not associated with ARE, although the maximum dose to the 5th nerve is a significant predictor of trigeminal dysfunction, with a threshold of 9 Gy. The overall 2-year tumor control rate was 96%. Conclusions: Target volume is the most important predictor of adverse radiation effects, and we identified the significant treatment volume threshold to be 5 cm3. We also established through our series that the maximum tolerable dose to the 5th nerve is 9 Gy.« less

Acute administration of tramadol and tapentadol at effective analgesic and maximum tolerated doses causes hepato- and nephrotoxic effects in Wistar rats.

PubMed

Barbosa, Joana; Faria, Juliana; Leal, Sandra; Afonso, Luís Pedro; Lobo, João; Queirós, Odília; Moreira, Roxana; Carvalho, Félix; Dinis-Oliveira, Ricardo Jorge

2017-08-15

Tramadol and tapentadol are two atypical synthetic opioid analgesics, with monoamine reuptake inhibition properties. Mainly aimed at the treatment of moderate to severe pain, these drugs are extensively prescribed for multiple clinical applications. Along with the increase in their use, there has been an increment in their abuse, and consequently in the reported number of adverse reactions and intoxications. However, little is known about their mechanisms of toxicity. In this study, we have analyzed the in vivo toxicological effects in liver and kidney resulting from an acute exposure of a rodent animal model to both opioids. Male Wistar rats were intraperitoneally administered with 10, 25 and 50mg/kg tramadol and tapentadol, corresponding to a low, effective analgesic dose, an intermediate dose and the maximum recommended daily dose, respectively, for 24h. Toxicological effects were assessed in terms of oxidative stress, biochemical and metabolic parameters and histopathology, using serum and urine samples, liver and kidney homogenates and tissue specimens. The acute exposure to tapentadol caused a dose-dependent increase in protein oxidation in liver and kidney. Additionally, exposure to both opioids led to hepatic commitment, as shown by increased serum lipid levels, decreased urea concentration, increased alanine aminotransferase and decreased butyrylcholinesterase activities. It also led to renal impairment, as reflected by proteinuria and decreased glomerular filtration rate. Histopathological findings included sinusoidal dilatation, microsteatosis, vacuolization, cell infiltrates and cell degeneration, indicating metabolic changes, inflammation and cell damage. In conclusion, a single effective analgesic dose or the maximum recommended daily dose of both opioids leads to hepatotoxicity and nephrotoxicity, with tapentadol inducing comparatively more toxicity. Whether these effects reflect risks during the therapeutic use or human overdoses requires focused attention by the medical community. Copyright © 2017 Elsevier B.V. All rights reserved.

SU-E-J-70: Evaluation of Multiple Isocentric Intensity Modulated and Volumetric Modulated Arc Therapy Techniques Using Portal Dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muralidhar, K Raja; Pangam, S; Kolla, J

2015-06-15

Purpose: To develop a method for verification of dose distribution in a patient during treatment using multiple isocentric Intensity modulated and volumetric modulated arc therapy techniques with portal dosimetry. Methods: Varian True Beam accelerator, equipped with an aS1000 megavoltage electronic portal imaging device (EPID) has an integrated image mode for portal dosimetry (PD). The source-to-imager distance was taken at 150 cm to avoid collision to the table. Fourteen fractions were analyzed for this study. During shift in a single plan from one isocenter to another isocenter, EPID also shifted longitudinally for each field by taking the extent of divergence ofmore » beam into the consideration for EPID distance of 150cm. Patients were given treatment everyday with EPID placed in proper position for each field. Several parameters were obtained by comparing the dose distribution between fractions to fraction. The impact of the intra-fraction and inter-fraction of the patient in combination with isocenter shift of the beams were observed. Results: During treatment, measurements were performed by EPID and were evaluated by the gamma method. Analysis was done between fractions for multiple isocenter treatments. The pass rates of the gamma analysis with a criterion of 3% and 3 mm for the 14 fractions were over 97.8% with good consistency. Whereas maximum gamma exceeded the criteria in few fractions (in<1 cc vol). Average gamma was observed in the criteria of 0.5%. Maximum dose difference and average dose differences were less than 0.22 CU and 0.01 CU for maximum tolerance of 1.0 CU and 0.2 CU respectively. Conclusion: EPID with extended distance is ideal method to verify the multiple isocentric dose distribution in patient during treatment, especially cold and hot spots in junction dose. Verification of shifts as well as the dose differences between each fraction due to inter-fraction and intra-fraction of the patient can be derived.« less

A novel design for a dose finding, safety, and drug interaction study of an antiepileptic drug (retigabine) in early clinical development.

PubMed

Sachdeo, Rajesh; Partiot, Arnaud; Biton, Victor; Rosenfeld, William E; Nohria, Virinder; Tompson, Debra; DeRossett, Sarah; Porter, Roger J

2014-06-01

To obtain information on the acceptable doses of the antiepileptic drug (AED) retigabine (RTG), the maximum tolerated dose (MTD), drug interactions, safety and tolerability, and preliminary evidence of efficacy when administered as adjunctive therapy and as monotherapy. Study 202 was an open-label, add-on study in patients with partial or generalized epilepsy treated with valproic acid (VPA), carbamazepine (CBZ), phenytoin (PHT), or topiramate (TPM) as monotherapy. Following baseline assessments, patients entered a dose titration phase of 28 – 56 days. The initial daily RTG dose was 100 or 200 mg (2 or 3 × daily). The RTG dose was increased every 1 - 2 weeks by 50 - 200 mg to a maximum of 1,600 mg/day. Once the RTG MTD had been attained, patients entered a 14-day maintenance period. Following this, the patient's background AED dose could be reduced, with the possibility of achieving RTG monotherapy. The final dosing regimen attained was maintained for an additional 14 days. Patients who completed study 202 could choose to continue treatment with RTG (with or without other AEDs) in study 208, the long-term extension of study 202. Safety assessments included adverse event (AE) monitoring, clinical laboratory evaluations, electrocardiograms, and physical and neurologic examinations. Patients' seizure diaries to assess the frequency and type of seizures, the percentage change in seizure rate, and the responder rate (>= 50% reduction in seizure rate from baseline) were evaluated. 60 patients (mean age 37.2, range 16 - 64 years) were enrolled in study 202, and 47 (78%) continued treatment with RTG in the extension study (208). In study 202, the most commonly reported AEs were: dizziness (53%), asthenia (42%), somnolence (33%), nausea (27%), speech disorder (27%), and tremor (27%). In the extension study, AEs were similar and included dizziness, somnolence, diplopia, feeling "drunk", confusion, fatigue, and dysarthria. The median percent reductions in 28-day seizure rate, relative to baseline in Studies 202 and 208, were ~ 20% and 47%, respectively. RTG did not alter the pharmacokinetics of the four monotherapy AEDs investigated. CBZ and PHT increased RTG clearance by 27% and 36%, respectively, whereas TPM and VPA had no effect on RTG clearance. Studies 202 and 208 provided critical information on RTG safety and tolerability, and reductions in seizure rates towards the design and conduct of subsequent pivotal clinical trials. Likewise, information regarding the appropriate dosage of RTG with VPA, CBZ, PHT, or TPM was obtained, which permitted the subsequent pivotal trials to be performed appropriately. *Currently at Shire Pharmaceuticals, Behavioral Health Business Unit, Wayne, PA, USA **Currently at University of Pennsylvania, Department of Neurology, Philadelphia, PA, USA.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Russell Feder and Mahmoud Z. Yousef

Neutronics analysis to find nuclear heating rates and personnel dose rates were conducted in support of the integration of diagnostics in to the ITER Upper Port Plugs. Simplified shielding models of the Visible-Infrared diagnostic and of the ECH heating system were incorporated in to the ITER global CAD model. Results for these systems are representative of typical designs with maximum shielding and a small aperture (Vis-IR) and minimal shielding with a large aperture (ECH). The neutronics discrete-ordinates code ATTILA® and SEVERIAN® (the ATTILA parallel processing version) was used. Material properties and the 500 MW D-T volume source were taken frommore » the ITER “Brand Model” MCNP benchmark model. A biased quadrature set equivelant to Sn=32 and a scattering degree of Pn=3 were used along with a 46-neutron and 21-gamma FENDL energy subgrouping. Total nuclear heating (neutron plug gamma heating) in the upper port plugs ranged between 380 and 350 kW for the Vis-IR and ECH cases. The ECH or Large Aperture model exhibited lower total heating but much higher peak volumetric heating on the upper port plug structure. Personnel dose rates are calculated in a three step process involving a neutron-only transport calculation, the generation of activation volume sources at pre-defined time steps and finally gamma transport analyses are run for selected time steps. ANSI-ANS 6.1.1 1977 Flux-to-Dose conversion factors were used. Dose rates were evaluated for 1 full year of 500 MW DT operation which is comprised of 3000 1800-second pulses. After one year the machine is shut down for maintenance and personnel are permitted to access the diagnostic interspace after 2-weeks if dose rates are below 100 μSv/hr. Dose rates in the Visible-IR diagnostic model after one day of shutdown were 130 μSv/hr but fell below the limit to 90 μSv/hr 2-weeks later. The Large Aperture or ECH style shielding model exhibited higher and more persistent dose rates. After 1-day the dose rate was 230 μSv/hr but was still at 120 μSv/hr 4-weeks later. __________________________________________________« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Russell E. Feder and Mahmoud Z. Youssef

Neutronics analysis to find nuclear heating rates and personnel dose rates were conducted in support of the integration of diagnostics in to the ITER Upper Port Plugs. Simplified shielding models of the Visible-Infrared diagnostic and of a large aperture diagnostic were incorporated in to the ITER global CAD model. Results for these systems are representative of typical designs with maximum shielding and a small aperture (Vis-IR) and minimal shielding with a large aperture. The neutronics discrete-ordinates code ATTILA® and SEVERIAN® (the ATTILA parallel processing version) was used. Material properties and the 500 MW D-T volume source were taken from themore » ITER “Brand Model” MCNP benchmark model. A biased quadrature set equivelant to Sn=32 and a scattering degree of Pn=3 were used along with a 46-neutron and 21-gamma FENDL energy subgrouping. Total nuclear heating (neutron plug gamma heating) in the upper port plugs ranged between 380 and 350 kW for the Vis-IR and Large Aperture cases. The Large Aperture model exhibited lower total heating but much higher peak volumetric heating on the upper port plug structure. Personnel dose rates are calculated in a three step process involving a neutron-only transport calculation, the generation of activation volume sources at pre-defined time steps and finally gamma transport analyses are run for selected time steps. ANSI-ANS 6.1.1 1977 Flux-to-Dose conversion factors were used. Dose rates were evaluated for 1 full year of 500 MW DT operation which is comprised of 3000 1800-second pulses. After one year the machine is shut down for maintenance and personnel are permitted to access the diagnostic interspace after 2-weeks if dose rates are below 100 μSv/hr. Dose rates in the Visible-IR diagnostic model after one day of shutdown were 130 μSv/hr but fell below the limit to 90 μSv/hr 2-weeks later. The Large Aperture style shielding model exhibited higher and more persistent dose rates. After 1-day the dose rate was 230 μSv/hr but was still at 120 μSv/hr 4-weeks later.« less

Dose responses for adaption to low doses of (60)Co gamma rays and (3)H beta particles in normal human fibroblasts.

PubMed

Broome, E J; Brown, D L; Mitchel, R E J

2002-08-01

The dose response for adaption to radiation at low doses was compared in normal human fibroblasts (AG1522) exposed to either (60)Co gamma rays or (3)H beta particles. Cells were grown in culture to confluence and exposed at either 37 degrees C or 0 degrees C to (3)H beta-particle or (60)Co gamma-ray adapting doses ranging from 0.1 mGy to 500 mGy. These cells, and unexposed control cells, were allowed to adapt during a fixed 3-h, 37 degrees C incubation prior to a 4-Gy challenge dose of (60)Co gamma rays. Adaption was assessed by measuring micronucleus frequency in cytokinesis-blocked, binucleate cells. No adaption was detected in cells exposed to (60)Co gamma radiation at 37 degrees C after a dose of 0.1 mGy given at a low dose rate or to 500 mGy given at a high dose rate. However, low-dose-rate exposure (1-3 mGy/min) to any dose between 1 and 500 mGy from either radiation, delivered at either temperature, caused cells to adapt and reduced the micronucleus frequency that resulted from the subsequent 4-Gy exposure. Within this dose range, the magnitude of the reduction was the same, regardless of the dose or radiation type. These results demonstrate that doses as low as (on average) about one track per cell (1 mGy) produce the same maximum adaptive response as do doses that deposit many tracks per cell, and that the two radiations were not different in this regard. Exposure at a temperature where metabolic processes, including DNA repair, were inactive (0 degrees C) did not alter the result, indicating that the adaptive response is not sensitive to changes in the accumulation of DNA damage within this range. The results also show that the RBE for low doses of tritium beta-particle radiation is 1, using adaption as the end point.

A phase I/II study of carfilzomib 2-10-min infusion in patients with advanced solid tumors.

PubMed

Papadopoulos, Kyriakos P; Burris, Howard A; Gordon, Michael; Lee, Peter; Sausville, Edward A; Rosen, Peter J; Patnaik, Amita; Cutler, Richard E; Wang, Zhengping; Lee, Susan; Jones, Suzanne F; Infante, Jeffery R

2013-10-01

Tolerability, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of carfilzomib, a selective proteasome inhibitor, administered twice weekly by 2-10-min intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 in 28-day cycles, were assessed in patients with advanced solid tumors in this phase I/II study. Adult patients with solid tumors progressing after ≥1 prior therapies were enrolled. The dose was 20 mg/m(2) in week 1 of cycle 1 and 20, 27, or 36 mg/m(2) thereafter. The maximum tolerated dose or protocol-defined maximum planned dose (MPD) identified during dose escalation was administered to an expansion cohort and to patients with small cell lung, non-small cell lung, ovarian, and renal cancer in phase II tumor-specific cohorts. Fourteen patients received carfilzomib during dose escalation. The single dose-limiting toxicity at 20/36 mg/m(2) was grade 3 fatigue, establishing the MPD as the expansion and phase II dose. Sixty-five additional patients received carfilzomib at the MPD. Adverse events included fatigue, nausea, anorexia, and dyspnea. Carfilzomib PK was dose proportional with a half-life <1 h. All doses resulted in at least 80 % proteasome inhibition in blood. Partial responses occurred in two patients in phase I, with 21.5 % stable disease after four cycles in evaluable patients in the expansion and phase II cohorts. Carfilzomib 20/36 mg/m(2) was well tolerated when administered twice weekly by 2-10-min IV infusion. At this dose and infusion rate, carfilzomib inhibited the proteasome in blood but demonstrated limited antitumor activity in patients with advanced solid tumors.

Side effects of methylphenidate in childhood cancer survivors: a randomized placebo-controlled trial.

PubMed

Conklin, Heather M; Lawford, Joanne; Jasper, Bruce W; Morris, E Brannon; Howard, Scott C; Ogg, Susan W; Wu, Shengjie; Xiong, Xiaoping; Khan, Raja B

2009-07-01

To investigate the frequency and severity of side effects of methylphenidate among childhood survivors of acute lymphoblastic leukemia and brain tumors and identify predictors of higher adverse effect levels. Childhood cancer survivors (N = 103) identified as having attention and learning problems completed a randomized, double-blind, 3-week, home-crossover trial of placebo, low-dose methylphenidate (0.3 mg/kg; 10 mg twice daily maximum) and moderate-dose methylphenidate (0.6 mg/kg; 20 mg twice daily maximum). Caregivers completed the Barkley Side Effects Rating Scale (SERS) at baseline and each week during the medication trial. Siblings of cancer survivors (N = 49) were recruited as a healthy comparison group. There was a significantly higher number and severity of symptoms endorsed on the SERS when patients were taking moderate dose compared with placebo or low dose, but not low dose compared with placebo. The number of side effects endorsed on the SERS was significantly lower during all 3 home-crossover weeks (placebo, low dose, moderate dose) when compared with baseline symptom scores. The severity of side effects was also significantly lower, compared with baseline screening, during placebo and low-dose weeks but not moderate-dose weeks. Both the number and severity of symptoms endorsed at baseline were significantly higher for patients compared with siblings. Female gender and lower IQ were associated with higher adverse effect levels. Methylphenidate is generally well tolerated by childhood cancer survivors. There is a subgroup at increased risk for side effects that may need to be closely monitored or prescribed a lower medication dose. The seemingly paradoxical findings of increased "side effects" at baseline must be considered when monitoring side effects and designing clinical trials.

Factors associated with higher oxytocin requirements in labor.

PubMed

Frey, Heather A; Tuuli, Methodius G; England, Sarah K; Roehl, Kimberly A; Odibo, Anthony O; Macones, George A; Cahill, Alison G

2015-09-01

To identify clinical characteristics associated with high maximum oxytocin doses in women who achieve complete cervical dilation. A retrospective nested case-control study was performed within a cohort of all term women at a single center between 2004 and 2008 who reached the second stage of labor. Cases were defined as women who had a maximum oxytocin dose during labor >20 mu/min, while women in the control group had a maximum oxytocin dose during labor of ≤20 mu/min. Exclusion criteria included no oxytocin administration during labor, multiple gestations, major fetal anomalies, nonvertex presentation, and prior cesarean delivery. Multiple maternal, fetal, and labor factors were evaluated with univariable analysis and multivariable logistic regression. Maximum oxytocin doses >20 mu/min were administered to 108 women (3.6%), while 2864 women received doses ≤20 mu/min. Factors associated with higher maximum oxytocin dose after adjusting for relevant confounders included maternal diabetes, birthweight >4000 g, intrapartum fever, administration of magnesium, and induction of labor. Few women who achieve complete cervical dilation require high doses of oxytocin. We identified maternal, fetal and labor factors that characterize this group of parturients.

Letrozole combined with low dose highly purified HMG for ovulation induction in clomiphene citrate-resistant infertile Chinese women with polycystic ovary syndrome: a prospective study.

PubMed

Zhao, Yue; Ruan, Xiangyan; Mueck, Alfred O

2017-06-01

There are still open questions about ovulation induction in clomiphene citrate-(CC)-resistant infertile women. Especially little is known about efficacy and safety of letrozole (LTZ) combined with low-dose highly purified human menopausal gonadotropin (Hp-HMG) in women with polycystic ovary syndrome (PCOS). Prospective, single-arm single-center trial in 200 infertile PCOS patients refractory for at least three CC-treatment cycles. Women with hyperandrogenism took Diane-35 for at least 3 months. All patients got LTZ on day 3 for 5 d in combination with Hp-HMG, starting with 75 IU from cycle day 7 and maintained for up to 3 d. The maximum dose was 150 IU. Primary end-points were ongoing and clinical pregnancy rate, secondary end-points mono-follicular development, ovulation rate, OHSS, multiple pregnancy and early pregnancy loss. Major safety end-point was the incidence of adverse events. Within 395 cycles the ongoing pregnancy rate was 28.24%, for cycles 35.23%, for patients 68%. The rate of ovulation per cycle was 97.7%, percentage of mono-follicular development 70.9%. No severe OHSS, multiple pregnancy, local or systemic side effects were seen. LTZ combined with low-dose Hp-HMG is an effective and safe choice for reducing hyperstimulation and increasing pregnancy rate in CC-resistant women with PCOS.

Estimates of internal-dose equivalent from inhalation and ingestion of selected radionuclides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dunning, D.E.

1982-01-01

This report presents internal radiation dose conversion factors for radionuclides of interest in environmental assessments of nuclear fuel cycles. This volume provides an updated summary of estimates of committed dose equivalent for radionuclides considered in three previous Oak Ridge National Laboratory (ORNL) reports. Intakes by inhalation and ingestion are considered. The International Commission on Radiological Protection (ICRP) Task Group Lung Model has been used to simulate the deposition and retention of particulate matter in the respiratory tract. Results corresponding to activity median aerodynamic diameters (AMAD) of 0.3, 1.0, and 5.0 ..mu..m are given. The gastorintestinal (GI) tract has been representedmore » by a four-segment catenary model with exponential transfer of radioactivity from one segment to the next. Retention of radionuclides in systemic organs is characterized by linear combinations of decaying exponential functions, recommended in ICRP Publication 30. The first-year annual dose rate, maximum annual dose rate, and fifty-year dose commitment per microcurie intake of each radionuclide is given for selected target organs and the effective dose equivalent. These estimates include contributions from specified source organs plus the systemic activity residing in the rest of the body; cross irradiation due to penetrating radiations has been incorporated into these estimates. 15 references.« less

The radiation dose from a proposed measurement of arsenic and selenium in human skin

NASA Astrophysics Data System (ADS)

Gherase, Mihai R.; Mader, Joanna E.; Fleming, David E. B.

2010-09-01

Dose measurements following 10 min irradiations with a portable x-ray fluorescence spectrometer composed of a miniature x-ray tube and a silicon PiN diode detector were performed using thermoluminescent dosimeters consisting of LiF:Mg,Ti chips of 3 mm diameter and 0.4 mm thickness. The table-top setup of the spectrometer was used for all measurements. The setup included a stainless steel lid which served as a radiation shield. Two rectangular polyethylene skin/soft tissue phantoms with two cylindrical plaster of Paris bone phantoms were used to study the effect of x-ray beam attenuation and backscatter on the measured dose. Eight different irradiation experiments were performed. The average dose rate values measured with TLD chips within a 1 × 1 cm2 area were between 4.8 and 12.8 mGy min-1. The equivalent dose for a 1 × 1 cm2 skin area was estimated to be 13.2 mSv. The maximum measured dose rate values with a single TLD chip were between 7.5 and 25.1 mGy min-1. The effective dose corresponding to a proposed arsenic/selenium skin measurement was estimated to be 0.13 µSv for a 2 min irradiation.

SU-E-P-47: Evaluation of Improvement of Esophagus Sparing in SBRT Lung Patients with Biologically Based IMRT Optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liang, X; Penagaricano, J; Paudel, N

2015-06-15

Purpose: To study the potential of improving esophageal sparing for stereotactic body radiation therapy (SBRT) lung cancer patients by using biological optimization (BO) compared to conventional dose-volume based optimization (DVO) in treatment planning. Methods: Three NSCLC patients (PTV (62.3cc, 65.1cc, and 125.1cc) adjacent to the heart) previously treated with SBRT were re-planned using Varian Eclipse TPS (V11) using DVO and BO. The prescription dose was 60 Gy in 5 fractions normalized to 95% of the PTV volume. Plans were evaluated by comparing esophageal maximum doses, PTV heterogeneity (HI= D5%/D95%), and Paddick’s conformity (CI) indices. Quality of the plans was assessedmore » by clinically-used IMRT QA procedures. Results: By using BO, the maximum dose to the esophagus was decreased 1384 cGy (34.6%), 502 cGy (16.5%) and 532 cGy (16.2%) in patient 1, 2 and 3 respectively. The maximum doses to spinal cord and the doses to 1000 cc and 1500 cc of normal lung were comparable in both plans. The mean doses (Dmean-hrt) and doses to 15cc of the heart (V15-hrt) were comparable for patient 1 and 2. However for patient 3, with the largest PTV, Dmean-hrt and V15-hrt increased by 62.2 cGy (18.3%) and 549.9 cGy (24.9%) respectively for the BO plans. The mean target HI of BO plans (1.13) was inferior to the DVO plans (1.07). The same trend was also observed for mean CI in BO plans (0.77) versus DVO plans (0.83). The QA pass rates (3%, 3mm) were comparable for both plans. Conclusion: This study demonstrated that the use of biological models in treatment planning optimization can substantially improve esophageal sparing without compromising spinal cord and normal lung doses. However, for the large PTV case (125.1cc) we studied here, Dmean-hrt and V15-hrt increased substantially. The target HI and CI were inferior in the BO plans.« less

Bladder/lung cancer mortality in Blackfoot-disease (BFD)-endemic area villages with low (<150 μg/L) well water arsenic levels--an exploration of the dose-response Poisson analysis.

PubMed

Lamm, Steven H; Robbins, Shayhan A; Zhou, Chao; Lu, Jun; Chen, Rusan; Feinleib, Manning

2013-02-01

To examine the analytic role of arsenic exposure on cancer mortality among the low-dose (well water arsenic level <150 μg/L) villages in the Blackfoot-disease (BFD) endemic area of southwest Taiwan and with respect to the southwest regional data. Poisson analyses of the bladder and lung cancer deaths with respect to arsenic exposure (μg/kg/day) for the low-dose (<150 μg/L) villages with exposure defined by the village median, mean, or maximum and with or without regional data. Use of the village median well water arsenic level as the exposure metric introduced misclassification bias by including villages with levels >500 μg/L, but use of the village mean or the maximum did not. Poisson analyses using mean or maximum arsenic levels showed significant negative cancer slope factors for models of bladder cancers and of bladder and lung cancers combined. Inclusion of the southwest Taiwan regional data did not change the findings when the model contained an explanatory variable for non-arsenic differences. A positive slope could only be generated by including the comparison population as a separate data point with the assumption of zero arsenic exposure from drinking water and eliminating the variable for non-arsenic risk factors. The cancer rates are higher among the low-dose (<150 μg/L) villages in the BFD area than in the southwest Taiwan region. However, among the low-dose villages in the BFD area, cancer risks suggest a negative association with well water arsenic levels. Positive differences from regional data seem attributable to non-arsenic ecological factors. Copyright © 2012 Elsevier Inc. All rights reserved.

Systemic glyceryl trinitrate reduces anal sphincter tone: is there a therapeutic indication?

PubMed

Connolly, C; Tierney, S; Grace, P

2018-05-01

Nitric oxide (NO) has diverse roles as a biological messenger. [1] Topically applied nitrate donors cause relaxation of the internal anal sphincter (IAS) and facilitate healing of anal fissures [2,3]. Systemic nitrates are commonly used for the treatment of ischaemic heart disease, yet the effects of systemically administered nitrates on the smooth muscle of the IAS are unknown. Our aim was to test the hypothesis that systemically administered nitrates at a normal dose, cause inhibition of anal sphincter activity. With fully informed consent, anal manometry was performed on nine volunteers. Maximum and mean anal resting pressure (representing the IAS), maximum squeeze pressure (representing the external anal sphincter), heart rate and blood pressure were measured, before and after administration of a normal 400 μg dose of sublingual glyceryl trinitrate spray. Data are expressed as mean (± standard error of the mean (SEM)). In four females and five males ranging from 19 to 50 years of age, administration of GTN resulted in a significant reduction in systolic blood pressure from 138 ± 5 to 127 ± 4 mmHg, P < 0.01. Mean resting pressure, over 5 min, was significantly reduced from 70 ± 10 to 62 ± 10 mmHg P < 0.05. The maximum resting pressure was also significantly reduced from 109 ± 12 to 86 ± 10 mmHg P = 0.04. Maximum squeeze pressure, heart rate and diastolic blood pressure were not significantly reduced. Systemic nitrates significantly inhibit internal anal sphincter function.

The effectiveness of reducing the daily dose of finasteride in men with benign prostatic hyperplasia

PubMed Central

Sullivan, Michael J; Geller, Jack

2002-01-01

Background Finasteride, a 5 alpha reductase inhibitor, is an established treatment for benign prostatic hyperplasia. The recommended dosage is 5 mg a day, however case reports have show effectiveness with lower doses. The objective of the current study was to determine in men with benign prostatic hyperplasia, previously treated for at least one year with finasteride 5 mg daily, if they will maintain subjective and objective improvements in urinary obstruction when treated with 2.5 mg of finasteride daily for one year. Methods In an open label, prospective study, 40 men with benign prostatic hyperplasia, previously treated for at least one year with 5 mg of finasteride, took 2.5 mg of finasteride daily for one year. Measurements included AUA symptom score, maximum flow rate, voided volume and PSA. Results There were no significant changes in maximum flow rate, voided volume, or AUA symptom score after one year of finasteride 2.5 mg daily therapy. PSA increased significantly, p < .01, after one year of finasteride 2.5 mg daily, 2.0 +1.4 ng/ml, when compared to finasteride 5 mg daily, 1.4+ 1.0 ng/ml. Conclusions The daily dose of finasteride can be reduced to 2.5 mg daily without significant effect on subjective and objective measures of urinary obstruction. Although statistically significant increases in PSA are noted when reducing the daily finasteride dose from 5 mg to 2.5 mg, the clinical significance of a mean .6 ng/ml increase in PSA is questionable. PMID:11818031

Characterization of a new transmission detector for patient individualized online plan verification and its influence on 6MV X-ray beam characteristics.

PubMed

Thoelking, Johannes; Sekar, Yuvaraj; Fleckenstein, Jens; Lohr, Frank; Wenz, Frederik; Wertz, Hansjoerg

2016-09-01

Online verification and 3D dose reconstruction on daily patient anatomy have the potential to improve treatment delivery, accuracy and safety. One possible implementation is to recalculate dose based on online fluence measurements with a transmission detector (TD) attached to the linac. This study provides a detailed analysis of the influence of a new TD on treatment beam characteristics. The influence of the new TD on surface dose was evaluated by measurements with an Advanced Markus Chamber (Adv-MC) in the build-up region. Based on Monte Carlo simulations, correction factors were determined to scale down the over-response of the Adv-MC close to the surface. To analyze the effects beyond dmax percentage depth dose (PDD), lateral profiles and transmission measurements were performed. All measurements were carried out for various field sizes and different SSDs. Additionally, 5 IMRT-plans (head & neck, prostate, thorax) and 2 manually created test cases (3×3cm(2) fields with different dose levels, sweeping gap) were measured to investigate the influence of the TD on clinical treatment plans. To investigate the performance of the TD, dose linearity as well as dose rate dependency measurements were performed. With the TD inside the beam an increase in surface dose was observed depending on SSD and field size (maximum of +11%, SSD = 80cm, field size = 30×30cm(2)). Beyond dmax the influence of the TD on PDDs was below 1%. The measurements showed that the transmission factor depends slightly on the field size (0.893-0.921 for 5×5cm(2) to 30×30cm(2)). However, the evaluation of clinical IMRT-plans measured with and without the TD showed good agreement after using a single transmission factor (γ(2%/2mm) > 97%, δ±3% >95%). Furthermore, the response of TD was found to be linear and dose rate independent (maximum difference <0.5% compared to reference measurements). When placed in the path of the beam, the TD introduced a slight, clinically acceptable increase of the skin dose even for larger field sizes and smaller SSDs and the influence of the detector on the dose beyond dmax as well as on clinical IMRT-plans was negligible. Since there was no dose rate dependency and the response was linear, the device is therefore suitable for clinical use. Only its absorption has to be compensated during treatment planning, either by the use of a single transmission factor or by including the TD in the incident beam model. Copyright © 2015. Published by Elsevier GmbH.

SU-F-T-461: Dosimetric Evaluation of Indigenous Farmer Type Chamber FAR65- GB for Reference Dosimetry of FFF MV Photon Beam

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patwe, P; Mhatre, V; Dandekar, P

Purpose: Indigenous Farmer type chamber FAR 65 GB is a reference class 0.6 cc ion chamber. It can be used for dosimetric evaluation of photon and high energy electron beams. We studied dosimetric characteristics of the chamber for 6MV and 10MV Flattening filter free FFF photon beams available on trueBEAM STx Linac. Methods: The study was carried out on trueBEAM STx Linac having 6 and 10 MV FFF photon beam with maximum dose rate 1400 and 2400 MU per min respectively. The dosimetric device to be evaluated is Rosalina Instruments FAR 65-GB Ion Chamber with active volume 0.65 cc, totalmore » active length 23.1cm, inner diameter of cylinder 6.2mm, wall thickness 0.4mm, inner electrode diameter 1mm. Inner and outer electrodes are made from Aluminium 2.7 gm per cc and graphite 1.82 gm per cc respectively. The ion chamber was placed along central axis of beam at 10cm depth and irradiated for 10cm × 10cm field size at SAD of 100 cm in plastic phantom. We studied Precision, Dose Linearity, Dose Rate dependence, directional dependence, Recombination effect. Recombination effect was determined using standard two-voltage method. Results: 1. Measurements were reproducible std deviation of 0.0105 and type A uncertainty 0.003265 under same set of reference conditions 2. Chamber exhibit dose linearity over a wider dose range. 3. Chamber shows dose rate independence for all available dose rate range. 4. Response of chamber with the angle of incidence of radiation is constant. 5. Recombination correction factors were 1.01848 and 1.02537 for dose rate 1400 and 2400 MU per min resp. Conclusion: Our study reveals that the chamber is prone to saturation effect at dose rate of 2400 MU per min. FAR 65-GB can be used for reference dosimetry of FFF MV photon beam with proper calculation of recombination effect.« less

Measurement of Individual Doses of Radiation by Personal Dosimeter Is Important for the Return of Residents from Evacuation Order Areas after Nuclear Disaster

PubMed Central

Orita, Makiko; Hayashida, Naomi; Taira, Yasuyuki; Fukushima, Yoshiko; Ide, Juichi; Endo, Yuuko; Kudo, Takashi; Yamashita, Shunichi; Takamura, Noboru

2015-01-01

To confirm the availability of individual dose evaluation for the return of residents after the accident at the Fukushima Dai-ichi Nuclear Power Plant (FNPP), we evaluated individual doses of radiation as measured by personal dosimeters in residents who temporarily stayed in Evacuation Order Areas in Kawauchi village, which is partially located within a 20 km radius of the FNPP. We also compared individual doses with the external radiation doses estimated from the ambient dose rates and with doses estimated from the concentrations of radionuclides in the soil around each individual’s house. Individual doses were significantly correlated with the ambient doses in front of the entrances to the houses (r = 0.90, p<0.01), in the backyards (r = 0.41, p<0.01) and in the nearby fields (r = 0.80, p<0.01). The maximum cumulative ambient doses in the backyards and fields around the houses were 6.38 and 9.27 mSv/y, respectively. The maximum cumulative individual dose was 3.28 mSv/y, and the median and minimum doses were 1.35 and 0.71 mSv/y. The estimated external effective doses from concentrations of artificial radionuclides in soil samples ranged from 0.03 to 23.42 mSv/y. The individual doses were moderately correlated with external effective doses in the backyards (r = 0.38, p<0.01) and in the fields (r = 0.36, p<0.01); however, the individual doses were not significantly correlated with the external effective doses in front of the entrances (r = 0.01, p = 0.92). Our study confirmed that individual doses are low levels even in the evacuation order area in Kawauchi village, and external effective dose levels are certainly decreasing due to the decay of artificial radionuclides and the decontamination of contaminated soil. Long-term follow-up of individual doses as well as internal-exposure doses, environmental monitoring and reconstruction of infrastructure are needed so that residents may return to their hometowns after a nuclear disaster. PMID:25806523

Measurement of individual doses of radiation by personal dosimeter is important for the return of residents from evacuation order areas after nuclear disaster.

PubMed

Orita, Makiko; Hayashida, Naomi; Taira, Yasuyuki; Fukushima, Yoshiko; Ide, Juichi; Endo, Yuuko; Kudo, Takashi; Yamashita, Shunichi; Takamura, Noboru

2015-01-01

To confirm the availability of individual dose evaluation for the return of residents after the accident at the Fukushima Dai-ichi Nuclear Power Plant (FNPP), we evaluated individual doses of radiation as measured by personal dosimeters in residents who temporarily stayed in Evacuation Order Areas in Kawauchi village, which is partially located within a 20 km radius of the FNPP. We also compared individual doses with the external radiation doses estimated from the ambient dose rates and with doses estimated from the concentrations of radionuclides in the soil around each individual's house. Individual doses were significantly correlated with the ambient doses in front of the entrances to the houses (r = 0.90, p<0.01), in the backyards (r = 0.41, p<0.01) and in the nearby fields (r = 0.80, p<0.01). The maximum cumulative ambient doses in the backyards and fields around the houses were 6.38 and 9.27 mSv/y, respectively. The maximum cumulative individual dose was 3.28 mSv/y, and the median and minimum doses were 1.35 and 0.71 mSv/y. The estimated external effective doses from concentrations of artificial radionuclides in soil samples ranged from 0.03 to 23.42 mSv/y. The individual doses were moderately correlated with external effective doses in the backyards (r = 0.38, p<0.01) and in the fields (r = 0.36, p<0.01); however, the individual doses were not significantly correlated with the external effective doses in front of the entrances (r = 0.01, p = 0.92). Our study confirmed that individual doses are low levels even in the evacuation order area in Kawauchi village, and external effective dose levels are certainly decreasing due to the decay of artificial radionuclides and the decontamination of contaminated soil. Long-term follow-up of individual doses as well as internal-exposure doses, environmental monitoring and reconstruction of infrastructure are needed so that residents may return to their hometowns after a nuclear disaster.

Maximum tolerated dose of nalmefene in patients receiving epidural fentanyl and dilute bupivacaine for postoperative analgesia.

PubMed

Dougherty, T B; Porche, V H; Thall, P F

2000-04-01

This study investigated the ability of the modified continual reassessment method (MCRM) to determine the maximum tolerated dose of the opioid antagonist nalmefene, which does not reverse analgesia in an acceptable number of postoperative patients receiving epidural fentanyl in 0.075% bupivacaine. In the postanesthetic care unit, patients received a single intravenous dose of 0.25, 0.50, 0.75, or 1.00 microg/kg nalmefene. Reversal of analgesia was defined as an increase in pain score of two or more integers above baseline on a visual analog scale from 0 through 10 after nalmefene administration. Patients were treated in cohorts of one, starting with the lowest dose. The maximum tolerated dose of nalmefene was defined as that dose, among the four studied, with a final mean probability of reversal of anesthesia (PROA) closest to 0.20 (ie., a 20% chance of causing reversal). The modified continual reassessment method is an iterative Bayesian statistical procedure that, in this study, selected the dose for each successive cohort as that having a mean PROA closest to the preselected target PROA of 0.20. The modified continual reassessment method repeatedly updated the PROA of each dose level as successive patients were observed for presence or absence of ROA. After 25 patients, the maximum tolerated dose of nalmefene was selected as 0.50 microg/kg (final mean PROA = 0.18). The 1.00-microg/kg dose was never tried because its projected PROA was far above 0.20. The modified continual reassessment method facilitated determination of the maximum tolerated dose ofnalmefene . Operating characteristics of the modified continual reassessment method suggest it may be an effective statistical tool for dose-finding in trials of selected analgesic or anesthetic agents.

A dosimetric analysis of intensity-modulated radiation therapy (IMRT) as an alternative to adjuvant high-dose-rate (HDR) brachytherapy in early endometrial cancer patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aydogan, Bulent; Mundt, Arno J.; Department of Radiation Oncology, University of Illinois at Chicago, Chicago, IL

2006-05-01

Purpose: To evaluate the role of intensity-modulated radiation treatment (IMRT) as an alternative to high-dose-rate (HDR) brachytherapy in the treatment of the vagina in postoperative early endometrial cancer patients after surgery. Methods and Materials: Planning computed tomography (CT) scans of 10 patients previously treated with HDR were used in this study. In all cases, a dose of 700 cGy/fraction was prescribed at a distance of 0.5 cm from the cylinder surface. The same CT scans were then used in IMRT planning. In this paradigm, the vaginal cylinder represents a component of a hypothetical immobilization system that would be indexed tomore » the linac treatment table. Results: Our study showed that IMRT provided relatively lower rectal doses than HDR when treatment was prescribed at a distance of 0.5 cm away from the cylinder surface. Maximum rectal doses were lower with IMRT compared with HDR (average: 89.0% vs. 142.6%, respectively, p < 0.05). Moreover, the mean rectal dose was lower in IMRT plans compared with HDR plans with treatment prescribed either to the surface (average: 14.8% vs. 21.4%, respectively, p < 0.05) or to 0.5 cm (average: 19.6% vs. 33.5%, respectively, p < 0.05). IMRT plans had planning target volume (PTV) coverage comparable with HDR (average PTV minimum for treatment prescribed to 0.5 cm: 93.9% vs. 92.1%, p = 0.71, respectively) with less inhomogeneity (average PTV maximum: 110.8% vs. 381.6%, p < 0.05). Conclusion: Our dosimetric analysis suggests that when used in conjunction with a suitable immobilization system, IMRT may provide an alternative to HDR brachytherapy in women with early endometrial cancer after hysterectomy. However, more studies are needed to evaluate the clinical merit of the IMRT in these patients.« less

Environmental radioactivity in the UK: the airborne geophysical view of dose rate estimates.

PubMed

Beamish, David

2014-12-01

This study considers UK airborne gamma-ray data obtained through a series of high spatial resolution, low altitude surveys over the past decade. The ground concentrations of the naturally occurring radionuclides Potassium, Thorium and Uranium are converted to air absorbed dose rates and these are used to assess terrestrial exposure levels from both natural and technologically enhanced sources. The high resolution airborne information is also assessed alongside existing knowledge from soil sampling and ground-based measurements of exposure levels. The surveys have sampled an extensive number of the UK lithological bedrock formations and the statistical information provides examples of low dose rate lithologies (the formations that characterise much of southern England) to the highest sustained values associated with granitic terrains. The maximum dose rates (e.g. >300 nGy h(-1)) encountered across the sampled granitic terrains are found to vary by a factor of 2. Excluding granitic terrains, the most spatially extensive dose rates (>50 nGy h(-1)) are found in association with the Mercia Mudstone Group (Triassic argillaceous mudstones) of eastern England. Geological associations between high dose rate and high radon values are also noted. Recent studies of the datasets have revealed the extent of source rock (i.e. bedrock) flux attenuation by soil moisture in conjunction with the density and porosity of the temperate latitude soils found in the UK. The presence or absence of soil cover (and associated presence or absence of attenuation) appears to account for a range of localised variations in the exposure levels encountered. The hypothesis is supported by a study of an extensive combined data set of dose rates obtained from soil sampling and by airborne geophysical survey. With no attenuation factors applied, except those intrinsic to the airborne estimates, a bias to high values of between 10 and 15 nGy h(-1) is observed in the soil data. A wide range of technologically enhanced, localised contributions to dose rate values are also apparent in the data sets. Two detailed examples are provided that reveal the detectability of site-scale environmental impacts due to former industrial activities and the high dose values (>500 nGy h(-1)) that are associated with former, small-scale Uranium mining operations. Copyright © 2014. Published by Elsevier Ltd.

In vivo thermoluminescence dosimetry dose verification of transperineal 192Ir high-dose-rate brachytherapy using CT-based planning for the treatment of prostate cancer.

PubMed

Anagnostopoulos, G; Baltas, D; Geretschlaeger, A; Martin, T; Papagiannis, P; Tselis, N; Zamboglou, N

2003-11-15

To evaluate the potential of in vivo thermoluminescence dosimetry to estimate the accuracy of dose delivery in conformal high-dose-rate brachytherapy of prostate cancer. A total of 50 LiF, TLD-100 cylindrical rods were calibrated in the dose range of interest and used as a batch for all fractions. Fourteen dosimeters for every treatment fraction were loaded in a plastic 4F catheter that was fixed in either one of the 6F needles implanted for treatment purposes or in an extra needle implanted after consulting with the patient. The 6F needles were placed either close to the urethra or in the vicinity of the median posterior wall of the prostate. Initial results are presented for 18 treatment fractions in 5 patients and compared to corresponding data calculated using the commercial treatment planning system used for the planning of the treatments based on CT images acquired postimplantation. The maximum observed mean difference between planned and delivered dose within a single treatment fraction was 8.57% +/- 2.61% (root mean square [RMS] errors from 4.03% to 9.73%). Corresponding values obtained after averaging results over all fractions of a patient were 6.88% +/- 4.93% (RMS errors from 4.82% to 7.32%). Experimental results of each fraction corresponding to the same patient point were found to agree within experimental uncertainties. Experimental results indicate that the proposed method is feasible for dose verification purposes and suggest that dose delivery in transperineal high-dose-rate brachytherapy after CT-based planning can be of acceptable accuracy.

Quality assurance of dynamic parameters in volumetric modulated arc therapy.

PubMed

Manikandan, A; Sarkar, B; Holla, R; Vivek, T R; Sujatha, N

2012-07-01

The purpose of this study was to demonstrate quality assurance checks for accuracy of gantry speed and position, dose rate and multileaf collimator (MLC) speed and position for a volumetric modulated arc treatment (VMAT) modality (Synergy S; Elekta, Stockholm, Sweden), and to check that all the necessary variables and parameters were synchronous. Three tests (for gantry position-dose delivery synchronisation, gantry speed-dose delivery synchronisation and MLC leaf speed and positions) were performed. The average error in gantry position was 0.5° and the average difference was 3 MU for a linear and a parabolic relationship between gantry position and delivered dose. In the third part of this test (sawtooth variation), the maximum difference was 9.3 MU, with a gantry position difference of 1.2°. In the sweeping field method test, a linear relationship was observed between recorded doses and distance from the central axis, as expected. In the open field method, errors were encountered at the beginning and at the end of the delivery arc, termed the "beginning" and "end" errors. For MLC position verification, the maximum error was -2.46 mm and the mean error was 0.0153 ±0.4668 mm, and 3.4% of leaves analysed showed errors of >±1 mm. This experiment demonstrates that the variables and parameters of the Synergy S are synchronous and that the system is suitable for delivering VMAT using a dynamic MLC.

In Vivo Absorption and Disposition of Cefadroxil after Escalating Oral Doses in Wild-Type and PepT1 Knockout Mice

PubMed Central

Posada, Maria M.; Smith, David E.

2013-01-01

Purpose To determine the effect of PepT1 on the absorption and disposition of cefadroxil, including the potential for saturable intestinal uptake, after escalating oral doses of drug. Methods The absorption and disposition kinetics of [3H]cefadroxil was determined in wild-type and PepT1 knockout mice after 44.5, 89.1, 178, and 356 nmol/g oral doses of drug. The pharmacokinetics of [3H]cefadroxil was also determined in both genotypes after 44.5 nmol/g intravenous bolus doses. Results PepT1 deletion reduced the area under the plasma concentration-time profile (AUC0-120) of cefadroxil by 10-fold, the maximum plasma concentration (Cmax) by 17.5-fold, and increased the time to reach a maximum plasma concentration (Tmax) by 3-fold. There was no evidence of nonlinear intestinal absorption since AUC0-120 and Cmax values changed in a dose-proportional manner. Moreover, the pharmacokinetics of cefadroxil was not different between genotypes after intravenous bolus doses, indicating that PepT1 did not affect drug disposition. Finally, no differences were observed in the peripheral tissue distribution of cefadroxil (i.e., outside gastrointestinal tract) once these tissues were corrected for differences in perfusing blood concentrations. Conclusions The findings demonstrate convincingly the critical role of intestinal PepT1 in both the rate and extent of oral administration for cefadroxil and potentially other aminocephalosporin drugs. PMID:23959853

A survival model for fractionated radiotherapy with an application to prostate cancer

NASA Astrophysics Data System (ADS)

Zaider, Marco; Zelefsky, Michael J.; Hanin, Leonid G.; Tsodikov, Alexander D.; Yakovlev, Andrei Y.; Leibel, Steven A.

2001-10-01

This paper explores the applicability of a mechanistic survival model, based on the distribution of clonogens surviving a course of fractionated radiation therapy, to clinical data on patients with prostate cancer. The study was carried out using data on 1100 patients with clinically localized prostate cancer who were treated with three-dimensional conformal radiation therapy. The patients were stratified by radiation dose (group 1: <67.5 Gy; group 2: 67.5-72.5 Gy; group 3: 72.5-77.5 Gy; group 4: 77.5-87.5 Gy) and prognosis category (favourable, intermediate and unfavourable as defined by pre-treatment PSA and Gleason score). A relapse was recorded when tumour recurrence was diagnosed or when three successive prostate specific antigen (PSA) elevations were observed from a post-treatment nadir PSA level. PSA relapse-free survival was used as the primary end point. The model, which is based on an iterated Yule process, is specified in terms of three parameters: the mean number of tumour clonogens that survive the treatment, the mean of the progression time of post-treatment tumour development and its standard deviation. The model parameters were estimated by the maximum likelihood method. The fact that the proposed model provides an excellent description both of the survivor function and of the hazard rate is prima facie evidence of the validity of the model because closeness of the two survivor functions (empirical and model-based) does not generally imply closeness of the corresponding hazard rates. The estimated cure probabilities for the favourable group are 0.80, 0.74 and 0.87 (for dose groups 1-3, respectively); for the intermediate group: 0.25, 0.51, 0.58 and 0.78 (for dose groups 1-4, respectively) and for the unfavourable group: 0.0, 0.27, 0.33 and 0.64 (for dose groups 1-4, respectively). The distribution of progression time to tumour relapse was found to be independent of prognosis group but dependent on dose. As the dose increases the mean progression time decreases (41, 28.5, 26.2 and 14.7 months for dose groups 1-4, respectively). This analysis confirms that, in terms of cure rate, dose escalation has a significant positive effect only in the intermediate and unfavourable groups. It was found that progression time is inversely proportional to dose, which means that patients recurring in higher dose groups have shorter recurrence times, yet these groups have better survival, particularly long-term. The explanation for this seemingly illogical observation lies in the fact that less aggressive tumours, potentially recurring after a long period of time, are cured by higher doses and do not contribute to the recurrence pattern. As a result, patients in higher dose groups are less likely to recur; however, if they do, they tend to recur earlier. The estimated hazard rates for prostate cancer pass through a clear-cut maximum, thus revealing a time period with especially high values of instantaneous cancer-specific risk; the estimates appear to be nonproportional across dose strata.

Luteal phase support in intrauterine insemination cycles: a prospective randomized study of 300 mg versus 600 mg intravaginal progesterone tablet.

PubMed

Biberoglu, Ebru H; Tanrıkulu, Filiz; Erdem, Mehmet; Erdem, Ahmet; Biberoglu, Kutay Omer

2016-01-01

Vaginal progesterone (P) has been suggested to be used for luteal phase support (LPS) in controlled ovarian stimulation (COH)-intrauterine insemination (IUI) cycles, however, no concensus exists about the best P dose. Therefore, considering the fecundability rate as the primary end point, our main objective was to find the optimal dose of P in COH-IUI cycles, comparing the two groups of women, each of which comprised of 100 women either on 300 mg or 600 mg of intravaginal P tablets, in a prospective randomized study design. The mean age of the women, duration of infertility, basal and day of hCG injection hormone levels in the female and sperm parameters were similar in the two study groups. Also, duration and dose of gonadotropin given, number of follicles, endometrial thickness, the total, ongoing and multiple pregnancy rates were comparable in both groups. We, therefore, claim that 300 mg of intravaginal micronized P should be the maximum dose of LPS in IUI cycles.

Skyshine photon doses from 6 and 10 MV medical linear accelerators

PubMed Central

da Rosa, Luiz A. R.

2012-01-01

The skyshine radiation phenomenon consists of the scattering of primary photon beams in the atmosphere above the roof of a medical linear accelerator facility, generating an additional dose at ground level in the vicinity of the treatment room. Thus, with respect to radioprotection, this situation plays an important role when the roof is designed with little shielding and there are buildings next to the radiotherapy treatment room. In literature, there are few reported skyshine‐measured doses and these contain poor agreement with empirical calculations. In this work, we carried out measurements of skyshine photon dose rates produced from eight different 6 and 10 MV medical accelerators. Each measurement was performed outside the room facility, with the beam positioned in the upward direction, at a horizontal distance from the target and for a 40 cm×40 cm maximum photon field size at the accelerator isocenter. Measured dose‐equivalent rates results were compared with calculations obtained by an empirical expression, and differences between them deviated in one or more order of magnitude. PACS numbers: 87.53.‐j, 87.53.Bn PMID:22231219

Georgia fishery study: implications for dose calculations. Revision 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Turcotte, M.D.S.

Fish consumption will contribute a major portion of the estimated individual and population doses from L-Reactor liquid releases and Cs-137 remobilization in Steel Creek. It is therefore important that the values for fish consumption used in dose calculations be as realistic as possible. Since publication of the L-Reactor Environmental Information Document (EID), data have become available on sport fishing in the Savannah River. These data provide SRP with a site-specific sport fish harvest and consumption values for use in dose calculations. The Georgia fishery data support the total population fish consumption and calculated dose reported in the EID. The datamore » indicate, however, that both the EID average and maximum individual fish consumption have been underestimated, although each to a different degree. The average fish consumption value used in the EID is approximately 3% below the lower limit of the fish consumption range calculated using the Georgia data. Maximum fish consumption in the EID has been underestimated by approximately 60%, and doses to the maximum individual should also be recalculated. Future dose calculations should utilize an average adult fish consumption value of 11.3 kg/yr, and a maximum adult fish consumption value of 34 kg/yr. Consumption values for the teen and child age groups should be increased proportionally: (1) teen average = 8.5; maximum = 25.9 kg/yr; and (2) child average = 3.6; maximum = 11.2 kg/yr. 8 refs.« less

Efficient Interplay Effect Mitigation for Proton Pencil Beam Scanning by Spot-Adapted Layered Repainting Evenly Spread out Over the Full Breathing Cycle.

PubMed

Poulsen, Per Rugaard; Eley, John; Langner, Ulrich; Simone, Charles B; Langen, Katja

2018-01-01

To develop and implement a practical repainting method for efficient interplay effect mitigation in proton pencil beam scanning (PBS). A new flexible repainting scheme with spot-adapted numbers of repainting evenly spread out over the whole breathing cycle (assumed to be 4 seconds) was developed. Twelve fields from 5 thoracic and upper abdominal PBS plans were delivered 3 times using the new repainting scheme to an ion chamber array on a motion stage. One time was static and 2 used 4-second, 3-cm peak-to-peak sinusoidal motion with delivery started at maximum inhalation and maximum exhalation. For comparison, all dose measurements were repeated with no repainting and with 8 repaintings. For each motion experiment, the 3%/3-mm gamma pass rate was calculated using the motion-convolved static dose as the reference. Simulations were first validated with the experiments and then used to extend the study to 0- to 5-cm motion magnitude, 2- to 6-second motion periods, patient-measured liver tumor motion, and 1- to 6-fraction treatments. The effect of the proposed method was evaluated for the 5 clinical cases using 4-dimensional (4D) dose reconstruction in the planning 4D computed tomography scan. The target homogeneity index, HI = (D 2 - D 98 )/D mean , of a single-fraction delivery is reported, where D 2 and D 98 is the dose delivered to 2% and 98% of the target, respectively, and D mean is the mean dose. The gamma pass rates were 59.6% ± 9.7% with no repainting, 76.5% ± 10.8% with 8 repaintings, and 92.4% ± 3.8% with the new repainting scheme. Simulations reproduced the experimental gamma pass rates with a 1.3% root-mean-square error and demonstrated largely improved gamma pass rates with the new repainting scheme for all investigated motion scenarios. One- and two-fraction deliveries with the new repainting scheme had gamma pass rates similar to those of 3-4 and 6-fraction deliveries with 8 repaintings. The mean HI for the 5 clinical cases was 14.2% with no repainting, 13.7% with 8 repaintings, 12.0% with the new repainting scheme, and 11.6% for the 4D dose without interplay effects. A novel repainting strategy for efficient interplay effect mitigation was proposed, implemented, and shown to outperform conventional repainting in experiments, simulations, and dose reconstructions. This strategy could allow for safe and more optimal clinical delivery of thoracic and abdominal proton PBS and better facilitate hypofractionated and stereotactic treatments. Copyright © 2017 Elsevier Inc. All rights reserved.

Results from different patient populations using combined therapy with alprostadil and sildenafil: predictors of satisfaction.

PubMed

Mydlo, J H; Volpe, M A; MacChia, R J

2000-09-01

To evaluate the outcome of combined therapy (using intraurethral alprostadil and oral sildenafil) in private and clinic patients with erectile dysfunction, and thus assess predictors of satisfaction. In all, 360 men were treated for erectile dysfunction using single and/or combined therapy, comprising 214 private-practice and 166 clinic patients. Responses were evaluated using the International Index for Erectile Function (IIEF) questionnaire before and after treatment. Serum testosterone levels, education and socio-economic status were also assessed. Group 1a consisted of 33 private patients and Group 1b of 24 clinic patients who tried the maximum dose of intraurethral alprostadil monotherapy initially, followed by the maximum dose of sildenafil monotherapy, and remained dissatisfied. Group 2a consisted of 32 private patients and group 2b of 31 clinic patients who tried the maximum dose of sildenafil monotherapy initially, followed by the maximum dose of alprostadil monotherapy, and were also dissatisfied. These two groups of 65 private and 55 clinic patients then underwent combined therapy. The mean (SD) score for erectile function was 24.1 (2) for combined therapy (a 123% improvement), and 19.8 (1. 8) (83% improvement) and 15.2 (1.6) (41% improvement) for sildenafil and alprostadil monotherapies (P < 0.05 for both patient groups). The men also reported an improvement in their satisfaction with intercourse. However, at 18 months, 60 of the 65 private patients but only 40 of the 55 clinic patients continued with combined therapy; thus, the discontinuation rate was three times greater among clinic than among private patients. Furthermore, the private patients had an overall improvement in the satisfaction score of 128%, compared with 51% for the clinic patients. Although there were no significant differences in erectile function improvement within the two satisfied combined therapy groups, the differences in overall satisfaction and long-term withdrawal rates suggests that other factors beside motivation must be involved for success, e.g. education, persistence, realistic expectations, and certain psychological factors. Combined therapy should be considered for those patients who have a suboptimal response to monotherapy and refuse or are not candidates for surgical options. Generally, those patients with a higher education, greater persistence and more realistic expectations were more satisfied with combined therapy.

Definition of Small Gram Quantity Contents for Type B Radioactive Material Transportation Packages: Activity-Based Content Limitations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sitaraman, S; Kim, S; Biswas, D

2010-10-27

Since the 1960's, the Department of Transportation Specification (DOT Spec) 6M packages have been used extensively for transportation of Type B quantities of radioactive materials between Department of Energy (DOE) facilities, laboratories, and productions sites. However, due to the advancement of packaging technology, the aging of the 6M packages, and variability in the quality of the packages, the DOT implemented a phased elimination of the 6M specification packages (and other DOT Spec packages) in favor of packages certified to meet federal performance requirements. DOT issued the final rule in the Federal Register on October 1, 2004 requiring that use ofmore » the DOT Specification 6M be discontinued as of October 1, 2008. A main driver for the change was the fact that the 6M specification packagings were not supported by a Safety Analysis Report for Packaging (SARP) that was compliant with Title 10 of the Code of Federal Regulations part 71 (10 CFR 71). Therefore, materials that would have historically been shipped in 6M packages are being identified as contents in Type B (and sometimes Type A fissile) package applications and addenda that are to be certified under the requirements of 10 CFR 71. The requirements in 10 CFR 71 include that the Safety Analysis Report for Packaging (SARP) must identify the maximum radioactivity of radioactive constituents and maximum quantities of fissile constituents (10 CFR 71.33(b)(1) and 10 CFR 71.33(b)(2)), and that the application (i.e., SARP submittal or SARP addendum) demonstrates that the external dose rate (due to the maximum radioactivity of radioactive constituents and maximum quantities of fissile constituents) on the surface of the packaging (i.e., package and contents) not exceed 200 mrem/hr (10 CFR 71.35(a), 10 CFR 71.47(a)). It has been proposed that a 'Small Gram Quantity' of radioactive material be defined, such that, when loaded in a transportation package, the dose rates at external points of an unshielded packaging not exceed the regulatory limits prescribed by 10 CFR 71 for non-exclusive shipments. The mass of each radioisotope presented in this paper is limited by the radiation dose rate on the external surface of the package, which per the regulatory limit should not exceed 200 mrem/hr. The results presented are a compendium of allowable masses of a variety of different isotopes (with varying impurity levels of beryllium in some of the actinide isotopes) that, when loaded in an unshielded packaging, do not result in an external dose rate on the surface of the package that exceeds 190 mrem/hr (190 mrem/hr was chosen to provide 5% conservatism relative to the regulatory limit). These mass limits define the term 'Small Gram Quantity' (SGQ) contents in the context of radioactive material transportation packages. The term SGQ is isotope-specific and pertains to contents in radioactive material transportation packages that do not require shielding and still satisfy the external dose rate requirements. Since these calculated mass limits are for contents without shielding, they are conservative for packaging materials that provide some limited shielding or if the contents are placed into a shielded package. The isotopes presented in this paper were chosen as the isotopes that Department of Energy (DOE) sites most likely need to ship. Other more rarely shipped isotopes, along with industrial and medical isotopes, are planned to be included in subsequent extensions of this work.« less

Evaluation of the dosimetric properties of a synthetic single crystal diamond detector in high energy clinical proton beams.

PubMed

Mandapaka, A K; Ghebremedhin, A; Patyal, B; Marinelli, Marco; Prestopino, G; Verona, C; Verona-Rinati, G

2013-12-01

To investigate the dosimetric properties of a synthetic single crystal diamond Schottky diode for accurate relative dose measurements in large and small field high-energy clinical proton beams. The dosimetric properties of a synthetic single crystal diamond detector were assessed by comparison with a reference Markus parallel plate ionization chamber, an Exradin A16 microionization chamber, and Exradin T1a ion chamber. The diamond detector was operated at zero bias voltage at all times. Comparative dose distribution measurements were performed by means of Fractional depth dose curves and lateral beam profiles in clinical proton beams of energies 155 and 250 MeV for a 14 cm square cerrobend aperture and 126 MeV for 3, 2, and 1 cm diameter circular brass collimators. ICRU Report No. 78 recommended beam parameters were used to compare fractional depth dose curves and beam profiles obtained using the diamond detector and the reference ionization chamber. Warm-up∕stability of the detector response and linearity with dose were evaluated in a 250 MeV proton beam and dose rate dependence was evaluated in a 126 MeV proton beam. Stem effect and the azimuthal angle dependence of the diode response were also evaluated. A maximum deviation in diamond detector signal from the average reading of less than 0.5% was found during the warm-up irradiation procedure. The detector response showed a good linear behavior as a function of dose with observed deviations below 0.5% over a dose range from 50 to 500 cGy. The detector response was dose rate independent, with deviations below 0.5% in the investigated dose rates ranging from 85 to 300 cGy∕min. Stem effect and azimuthal angle dependence of the diode signal were within 0.5%. Fractional depth dose curves and lateral beam profiles obtained with the diamond detector were in good agreement with those measured using reference dosimeters. The observed dosimetric properties of the synthetic single crystal diamond detector indicate that its behavior is proton energy independent and dose rate independent in the investigated energy and dose rate range and it is suitable for accurate relative dosimetric measurements in large as well as in small field high energy clinical proton beams.

Dosimetric effects of Onyx embolization on Gamma Knife arteriovenous malformation dose distributions.

PubMed

Schlesinger, David J; Nordström, Håkan; Lundin, Anders; Xu, Zhiyuan; Sheehan, Jason P

2016-12-01

OBJECTIVE Patients with arteriovenous malformations (AVMs) treated with Gamma Knife radiosurgery (GKRS) subsequent to embolization suffer from elevated local failure rates and differences in adverse radiation effects. Onyx is a common embolic material for AVMs. Onyx is formulated with tantalum, a high atomic number (Z = 73) element that has been investigated as a source of dosimetric uncertainty contributing to the less favorable clinical results. However, prior studies have not modeled the complicated anatomical and beam geometries characteristic of GKRS. This study investigated the magnitude of dose perturbation that can occur due to Onyx embolization using clinically realistic anatomical and Gamma Knife beam models. METHODS Leksell GammaPlan (LGP) was used to segment the AVM nidus and areas of Onyx from postcontrast stereotactic MRI for 7 patients treated with GKRS postembolization. The resulting contours, skull surface, and clinically selected dose distributions were exported from LGP in DICOM-RT (Digital Imaging and Communications in Medicine-radiotherapy) format. Isocenter locations and dwell times were recorded from the LGP database. Contours were converted into 3D mesh representations using commercial and in-house mesh-editing software. The resulting data were imported into a Monte Carlo (MC) dose calculation engine (Pegasos, Elekta Instruments AB) with a beam geometry for the Gamma Knife Perfexion. The MC-predicted dose distributions were calculated with Onyx assigned manufacturer-reported physical constants (MC-Onyx), and then compared with corresponding distributions in which Onyx was reassigned constants for water (MC-water). Differences in dose metrics were determined, including minimum, maximum, and mean dose to the AVM nidus; selectivity index; and target coverage. Combined differences in dose magnitude and distance to agreement were calculated as 3D Gamma analysis passing rates using tolerance criteria of 0.5%/0.5 mm, 1.0%/1.0 mm, and 3.0%/3.0 mm. RESULTS Overall, the mean percentage differences in dose metrics for MC-Onyx relative to MC-water were as follows; all data are reported as mean (SD): minimum dose to AVM = -0.7% (1.4%), mean dose to AVM = 0.1% (0.2%), maximum dose to AVM = 2.9% (5.0%), selectivity = 0.1% (0.2%), and coverage = -0.0% (0.2%). The mean percentage of voxels passing at each Gamma tolerance were as follows: 99.7% (0.1%) for 3.0%/3.0 mm, 98.2% (0.7%) for 1.0%/1.0 mm, and 52.1% (4.4%) for 0.5%/0.5 mm. CONCLUSIONS Onyx embolization appears to have a detectable effect on the delivered dose distribution. However, the small changes in dose metrics and high Gamma passing rates at 1.0%/1.0 mm tolerance suggest that these changes are unlikely to be clinically significant. Additional sources of delivery and biological uncertainty should be investigated to determine the root cause of the observed less favorable postembolization GKRS outcomes.

An Interlaboratory Comparison of Dosimetry for a Multi-institutional Radiobiological

PubMed Central

Seed, TM; Xiao, S; Manley, N; Nikolich-Zugich, J; Pugh, J; van den Brink, M; Hirabayashi, Y; Yasutomo, K; Iwama, A; Koyasu, S; Shterev, I; Sempowski, G; Macchiarini, F; Nakachi, K; Kunugi, KC; Hammer, CG; DeWerd, LA

2016-01-01

Purpose An interlaboratory comparison of radiation dosimetry was conducted to determine the accuracy of doses being used experimentally for animal exposures within a large multi-institutional research project. The background and approach to this effort are described and discussed in terms of basic findings, problems and solutions. Methods Dosimetry tests were carried out utilizing optically stimulated luminescence (OSL) dosimeters embedded midline into mouse carcasses and thermal luminescence dosimeters (TLD) embedded midline into acrylic phantoms. Results The effort demonstrated that the majority (4/7) of the laboratories was able to deliver sufficiently accurate exposures having maximum dosing errors of ≤ 5%. Comparable rates of ‘dosimetric compliance’ were noted between OSL- and TLD-based tests. Data analysis showed a highly linear relationship between ‘measured’ and ‘target’ doses, with errors falling largely between 0–20%. Outliers were most notable for OSL-based tests, while multiple tests by ‘non-compliant’ laboratories using orthovoltage x-rays contributed heavily to the wide variation in dosing errors. Conclusions For the dosimetrically non-compliant laboratories, the relatively high rates of dosing errors were problematic, potentially compromising the quality of ongoing radiobiological research. This dosimetry effort proved to be instructive in establishing rigorous reviews of basic dosimetry protocols ensuring that dosing errors were minimized. PMID:26857121

An interlaboratory comparison of dosimetry for a multi-institutional radiobiological research project: Observations, problems, solutions and lessons learned.

PubMed

Seed, Thomas M; Xiao, Shiyun; Manley, Nancy; Nikolich-Zugich, Janko; Pugh, Jason; Van den Brink, Marcel; Hirabayashi, Yoko; Yasutomo, Koji; Iwama, Atsushi; Koyasu, Shigeo; Shterev, Ivo; Sempowski, Gregory; Macchiarini, Francesca; Nakachi, Kei; Kunugi, Keith C; Hammer, Clifford G; Dewerd, Lawrence A

2016-01-01

An interlaboratory comparison of radiation dosimetry was conducted to determine the accuracy of doses being used experimentally for animal exposures within a large multi-institutional research project. The background and approach to this effort are described and discussed in terms of basic findings, problems and solutions. Dosimetry tests were carried out utilizing optically stimulated luminescence (OSL) dosimeters embedded midline into mouse carcasses and thermal luminescence dosimeters (TLD) embedded midline into acrylic phantoms. The effort demonstrated that the majority (4/7) of the laboratories was able to deliver sufficiently accurate exposures having maximum dosing errors of ≤5%. Comparable rates of 'dosimetric compliance' were noted between OSL- and TLD-based tests. Data analysis showed a highly linear relationship between 'measured' and 'target' doses, with errors falling largely between 0 and 20%. Outliers were most notable for OSL-based tests, while multiple tests by 'non-compliant' laboratories using orthovoltage X-rays contributed heavily to the wide variation in dosing errors. For the dosimetrically non-compliant laboratories, the relatively high rates of dosing errors were problematic, potentially compromising the quality of ongoing radiobiological research. This dosimetry effort proved to be instructive in establishing rigorous reviews of basic dosimetry protocols ensuring that dosing errors were minimized.

A new biostimulation approach based on the concept of remaining P for soil bioremediation.

PubMed

Júlio, Aline Daniela Lopes; Fernandes, Rita de Cássia Rocha; Costa, Maurício Dutra; Neves, Júlio César Lima; Rodrigues, Edmo Montes; Tótola, Marcos Rogério

2018-02-01

C:N:P ratio is generally adopted to estimate the amount of nitrogen and phosphorus to be added to soils to accelerate biodegradation of organic contaminants. However, differences in P fixation among soils lead to varying amounts of available P when a specific dose of the element is applied to different soils. Thus, the application of fertilizers to achieve a previously established C:P ratio leads to biodegradation rates that can be lower than the theoretical maximum. In this study, we developed an equation to estimate the dose of P required to maximize organic contaminant biodegradation in soils as a function of remaining P (P-rem), using diesel as a model contaminant. The soils were contaminated with diesel and received six doses of P. CO 2 emission was used to estimate biodegradation of hydrocarbons. Biodegradation increased with P doses. The P level that provided the highest hydrocarbon biodegradation rate showed linear and negative correlation with P-rem. The result shows that the requirement for P decreases as the P-rem of the soil increases (or the P-fixing capacity decreases). The dose of P recommended to maximize hydrocarbon biodegradation rate in soil can be estimated by the formula P (mg/dm 3 ) = 436.5-5.39 × P-rem (mg/L). Copyright © 2017 Elsevier Ltd. All rights reserved.

Pharmacokinetic profile of nifedipine GITS in hypertensive patients with chronic renal impairment.

PubMed

Schneider, R; Stolero, D; Griffel, L; Kobelt, R; Brendel, E; Iaina, A

1994-01-01

25 hypertensive patients with normal or impaired renal function underwent pharmacokinetic and safety studies after single and multiple dose administration of nifedipine GITS (Gastro-Intestinal Therapeutic System) 60mg tablets. Complete pharmacokinetic data were obtained from 23 of these patients. Blood pressure and heart rate changes were compatible with the known properties of the drug. Impaired renal function did not affect the maximum plasma concentrations or bioavailability of nifedipine after single or multiple dose administration of nifedipine GITS, nor was there any evidence of excessive drug accumulation in the presence of renal impairment.

Assessing exposure to granite countertops--Part 1: Radiation.

PubMed

Myatt, Theodore A; Allen, Joseph G; Minegishi, Taeko; McCarthy, William B; Stewart, James H; Macintosh, David L; McCarthy, John F

2010-05-01

Humans are continuously exposed to low levels of ionizing radiation. Known sources include radon, soil, cosmic rays, medical treatment, food, and building products such as gypsum board and concrete. Little information exists about radiation emissions and associated doses from natural stone finish materials such as granite countertops in homes. To address this knowledge gap, gross radioactivity, gamma ray activity, and dose rate were determined for slabs of granite marketed for use as countertops. Annual effective radiation doses were estimated from measured dose rates and human activity patterns while accounting for the geometry of granite countertops in a model kitchen. Gross radioactivity, gamma activity, and dose rate varied significantly among and within slabs of granite with ranges for median levels at the slab surface of ND to 3000 cpm, ND to 98,000 cpm, and ND to 1.5E-4 mSv/h, respectively. The maximum activity concentrations of the (40)K, (232)Th, and (226)Ra series were 2715, 231, and 450 Bq/kg, respectively. The estimated annual radiation dose from spending 4 h/day in a hypothetical kitchen ranged from 0.005 to 0.18 mSv/a depending on the type of granite. In summary, our results show that the types of granite characterized in this study contain varying levels of radioactive isotopes and that their observed emissions are consistent with those reported in the scientific literature. We also conclude from our analyses that these emissions are likely to be a minor source of external radiation dose when used as countertop material within the home and present a negligible risk to human health.

Low-Temperature Desorption of N2O from NO on Rutile TiO2(110)-1x1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Boseong; Li, Zhenjun; Kay, Bruce D.

2014-05-08

We find that NO dosed on rutile TiO2(110)-1×1 at substrate temperatures as low as 50 K readily reacts to produce N2O which desorbs promptly from the surface leaving an oxygen adatom behind. The desorption rate of N2O reaches a maximum value after 1 – 2 sec at an NO flux of 1.2 ×1014 NO/cm2∙sec and then decreases rapidly as the initially clean, reduced TiO2(110) surface with ~5% oxygen vacancies (VO’s) becomes covered with oxygen adatoms and unreacted NO. The maximum desorption rate is also found to increase as the substrate temperature is raised up to about 100 K. Interestingly, themore » N2O desorption during the low-temperature (LT) NO dose is strongly suppressed when molecular oxygen is predosed, whereas it persists on the surface with VO’s passivated by surface hydroxyls. Our results show that the surface charge, not the VO sites, plays a dominant role in the LT N2O desorption induced by a facile NO reduction at such low temperatures.« less

Studies on the bronchodilator, tremorogenic, cardiovascular and hypokalaemic effects of fenoterol dry powder in asthma.

PubMed Central

Bauer, K G; Kaik, B; Sertl, K; Kaik, G A

1993-01-01

1. The airway and tremor response and cardiovascular and hypokalaemic effects of single and cumulative doses of fenoterol given by dry powder capsules (DPC) and by metered dose inhaler (MDI) were studied in asthmatics in two randomized, crossover trials. 2. Single doses of fenoterol DPC and MDI (0.2 mg, 0.4 mg), investigated in 24 subjects, produced similar, dose-dependent increases in FEV1. Fenoterol DPC caused less tremor response and less hypokalaemic effects than fenoterol MDI. 3. Cumulative doses of fenoterol DPC and MDI (0.2, 0.6, 1.4, 3.0, 6.2 mg), investigated in 12 subjects, produced a comparable bronchodilatation (mean maximum increase in FEV1 was 0.53 +/- 0.06/0.52 +/- 0.081 for DPC/MDI) and a similar, dose-dependent rise in heart rate (35 +/- 3.81/41 +/- 2.25 beats min(-1)). The rise in tremor and the fall in plasma potassium were smaller after DPC than after MDI. The mean maximum changes were 51.58 +/- 6.41/95.83 +/- 6.75 cm s(-2) for tremor and -0.68 +/- 0.09/-0.96 +/- 0.10 mmol l(-1) for potassium. 4. Our findings may result from a difference in the pharmacokinetics of the dry powder and the aerosol formulation, particularly differences in distribution and absorption. 5. In conclusion, fenoterol DPC used in low therapeutic doses (0.2,0.4 mg), is preferable to the MDI. Fenoterol DPC used as rescue medication in high cumulative doses, do not suggest a greater safety margin than the MDI and the same restrictions should be considered for the fenoterol dry powder formulation as suggested for the MDI. PMID:12959305

Assessment of diurnal systemic dose of agrochemicals in regulatory toxicity testing--an integrated approach without additional animal use.

PubMed

Saghir, Shakil A; Bartels, Michael J; Rick, David L; McCoy, Alene T; Rasoulpour, Reza J; Ellis-Hutchings, Robert G; Sue Marty, M; Terry, Claire; Bailey, Jason P; Billington, Richard; Bus, James S

2012-07-01

Integrated toxicokinetics (TK) data provide information on the rate, extent and duration of systemic exposure across doses, species, strains, gender, and life stages within a toxicology program. While routine for pharmaceuticals, TK assessments of non-pharmaceuticals are still relatively rare, and have never before been included in a full range of guideline studies for a new agrochemical. In order to better understand the relationship between diurnal systemic dose (AUC(24h)) and toxicity of agrochemicals, TK analyses in the study animals is now included in all short- (excluding acute), medium- and long-term guideline mammalian toxicity studies including reproduction/developmental tests. This paper describes a detailed procedure for the implementation of TK in short-, medium- and long-term regulatory toxicity studies, without the use of satellite animals, conducted on three agrochemicals (X11422208, 2,4-D and X574175). In these studies, kinetically-derived maximum doses (KMD) from short-term studies instead of, or along with, maximum tolerated doses (MTD) were used for the selection of the high dose in subsequent longer-term studies. In addition to leveraging TK data to guide dose level selection, the integrated program was also used to select the most appropriate method of oral administration (i.e., gavage versus dietary) of test materials for rat and rabbit developmental toxicity studies. The integrated TK data obtained across toxicity studies (without the use of additional/satellite animals) provided data critical to understanding differences in response across doses, species, strains, sexes, and life stages. Such data should also be useful in mode of action studies and to improve human risk assessments. Copyright © 2012 Elsevier Inc. All rights reserved.

Effect of heating rate on thermoluminescence output of LiF: Mg, Ti (TLD-100) in dosimetric applications

NASA Astrophysics Data System (ADS)

Singh, Ranjit; Kainth, Harpreet Singh

2018-07-01

The luminiscence characteristics of thermoluminscence dosimeter LiF: Mg, Ti (TLD-100) irradiated to X-rays from 6 MV linac have been studied for wide range of 2-50 K/s readout linear heating rates. The reproducibility of glow curves for TLDs is found to be better at lower heating rates and depreciate at higher heating rates. The glow curve spectra were analysed using deconvolution procedure based on general-order kinetics. Shift in the peak maximum temperature per unit rise in heating rate for various peaks were found to decrease with heating rate. The TLDs irradiated with same dose exhibit decreasing TL counts with increase in the heating rate, which indicate the thermal quenching effect in TLD-100. The value of activation energy for each peak within the glow curve increases with heating rate. Calibration curves plotted for the dose range 0.4-1020 cGy exhibit decreasing slope with increasing readout heating rate. Corrections for temperature lag between the heating element and the dosimeter, and the effective heating rate (βeff) across the sample estimated using formulation proposed by Kitis and Tuyn and are found to be fairly applicable.

Results on Dose Distributions in a Human Body from the Matroshka-R Experiment onboard the ISS Obtained with the Tissue-Equivalent Spherical Phantom

NASA Astrophysics Data System (ADS)

Shurshakov, Vyacheslav; Nikolaev, Igor; Kartsev, Ivan; Tolochek, Raisa; Lyagushin, Vladimir

The tissue-equivalent spherical phantom (32 kg mass, 35 cm diameter and 10 cm central spherical cave) made in Russia has been used on board the ISS in Matroshka-R experiment for more than 10 years. Both passive and active space radiation detectors can be located inside the phantom and on its surface. Due to the specially chosen phantom shape and size, the chord length distributions of the detector locations are attributed to self-shielding properties of the critical organs in a human body. Originally the spherical phantom was installed in the star board crew cabin of the ISS Service Module, then in the Piers-1, MIM-2, and MIM-1 modules of the ISS Russian segment, and finally in JAXA Kibo module. Total duration of the detector exposure is more than 2000 days in 9 sessions of the space experiment. In the first phase of the experiment with the spherical phantom the dose measurements were realized with only passive detectors (thermoluminescent and solid state track detectors). The detectors are placed inside the phantom along the axes of 20 containers and on the phantom outer surface in 32 pockets of the phantom jacket. After each session the passive detectors are returned to the ground. The results obtained show the dose difference on the phantom surface as much as a factor of 2, the highest dose being usually observed close to the outer wall of the compartment, and the lowest dose being in the opposite location along the phantom diameter. However, because of the ISS module shielding properties an inverse dose distribution in a human body can be observed when the dose rate maximum is closer to the geometrical center of the module. Maximum dose rate measured in the phantom is obviously due to the action of two radiation sources, namely, galactic cosmic rays (GCR) and Earth’ radiation belts. Minimum dose rate is produced mainly by the strongly penetrating GCR particles and is mostly observed behind more than 5 g/cm2 tissue shielding. Critical organ doses, mean-tissue and effective doses of a crew member in the ISS compartments are also estimated with the spherical phantom data. The estimated effective dose rate is found to be from 10 % to 15 % lower than the averaged dose on the phantom surface as dependent on the attitude of the critical organs. If compared with the anthropomorphic phantom Rando used inside and outside the ISS earlier, the Matroshka-R space experiment spherical phantom has lower mass, smaller size, and requires less crew time for the detector installation/retrieval; its tissue-equivalent properties are closer to the standard human body tissue than the Rando-phantom material. New sessions with the two tissue-equivalent phantoms are of great interest. Development of modified passive and active detector sets is in progress for the future ISS expeditions. Both the spherical and Rando-type phantoms proved their effectiveness to measure the critical organ doses and effective doses in-flight and if supplied with modernized dosimeters can be recommended for future exploratory manned missions to monitor continuously the crew exposure to space radiation.

FDA-sunlamp recommended Maximum Timer Interval And Exposure Schedule: consensus ISO/CIE dose equivalence.

PubMed

Dowdy, John C; Czako, Eugene A; Stepp, Michael E; Schlitt, Steven C; Bender, Gregory R; Khan, Lateef U; Shinneman, Kenneth D; Karos, Manuel G; Shepherd, James G; Sayre, Robert M

2011-09-01

The authors compared calculations of sunlamp maximum exposure times following current USFDA Guidance Policy on the Maximum Timer Interval and Exposure Schedule, with USFDA/CDRH proposals revising these to equivalent erythemal exposures of ISO/CIE Standard Erythema Dose (SED). In 2003, [USFDA/CDRH proposed replacing their unique CDRH/Lytle] erythema action spectrum with the ISO/CIE erythema action spectrum and revising the sunlamp maximum exposure timer to 600 J m(-2) ISO/CIE effective dose, presented as being biologically equivalent. Preliminary analysis failed to confirm said equivalence, indicating instead ∼38% increased exposure when applying these proposed revisions. To confirm and refine this finding, a collaboration of tanning bed and UV lamp manufacturers compiled 89 UV spectra representing a broad sampling of U.S. indoor tanning equipment. USFDA maximum recommended exposure time (Te) per current sunlamp guidance and CIE erythemal effectiveness per ISO/CIE standard were calculated. The CIE effective dose delivered per Te averaged 456 J(CIE) m(-2) (SD = 0.17) or ∼4.5 SED. The authors found that CDRH's proposed 600 J(CIE) m(-2) recommended maximum sunlamp exposure exceeds current Te erythemal dose by ∼33%. The current USFDA 0.75 MED initial exposure was ∼0.9 SED, consistent with 1.0 SED initial dose in existing international sunlamp standards. As no sunlamps analyzed exceeded 5 SED, a revised maximum exposure of 500 J(CIE) m(-2) (∼80% of CDRH's proposal) should be compatible with existing tanning equipment. A tanning acclimatization schedule is proposed beginning at 1 SED thrice-weekly, increasing uniformly stepwise over 4 wk to a 5 SED maximum exposure in conjunction with a tan maintenance schedule of twice-weekly 5 SED sessions, as biologically equivalent to current USFDA sunlamp policy.

Four-dimensional dose distributions of step-and-shoot IMRT delivered with real-time tumor tracking for patients with irregular breathing: Constant dose rate vs dose rate regulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang Xiaocheng; Han-Oh, Sarah; Gui Minzhi

2012-09-15

Purpose: Dose-rate-regulated tracking (DRRT) is a tumor tracking strategy that programs the MLC to track the tumor under regular breathing and adapts to breathing irregularities during delivery using dose rate regulation. Constant-dose-rate tracking (CDRT) is a strategy that dynamically repositions the beam to account for intrafractional 3D target motion according to real-time information of target location obtained from an independent position monitoring system. The purpose of this study is to illustrate the differences in the effectiveness and delivery accuracy between these two tracking methods in the presence of breathing irregularities. Methods: Step-and-shoot IMRT plans optimized at a reference phase weremore » extended to remaining phases to generate 10-phased 4D-IMRT plans using segment aperture morphing (SAM) algorithm, where both tumor displacement and deformation were considered. A SAM-based 4D plan has been demonstrated to provide better plan quality than plans not considering target deformation. However, delivering such a plan requires preprogramming of the MLC aperture sequence. Deliveries of the 4D plans using DRRT and CDRT tracking approaches were simulated assuming the breathing period is either shorter or longer than the planning day, for 4 IMRT cases: two lung and two pancreatic cases with maximum GTV centroid motion greater than 1 cm were selected. In DRRT, dose rate was regulated to speed up or slow down delivery as needed such that each planned segment is delivered at the planned breathing phase. In CDRT, MLC is separately controlled to follow the tumor motion, but dose rate was kept constant. In addition to breathing period change, effect of breathing amplitude variation on target and critical tissue dose distribution is also evaluated. Results: Delivery of preprogrammed 4D plans by the CDRT method resulted in an average of 5% increase in target dose and noticeable increase in organs at risk (OAR) dose when patient breathing is either 10% faster or slower than the planning day. In contrast, DRRT method showed less than 1% reduction in target dose and no noticeable change in OAR dose under the same breathing period irregularities. When {+-}20% variation of target motion amplitude was present as breathing irregularity, the two delivery methods show compatible plan quality if the dose distribution of CDRT delivery is renormalized. Conclusions: Delivery of 4D-IMRT treatment plans, stemmed from 3D step-and-shoot IMRT and preprogrammed using SAM algorithm, is simulated for two dynamic MLC-based real-time tumor tracking strategies: with and without dose-rate regulation. Comparison of cumulative dose distribution indicates that the preprogrammed 4D plan is more accurately and efficiently conformed using the DRRT strategy, as it compensates the interplay between patient breathing irregularity and tracking delivery without compromising the segment-weight modulation.« less

Modification and validation of an analytical source model for external beam radiotherapy Monte Carlo dose calculations.

PubMed

Davidson, Scott E; Cui, Jing; Kry, Stephen; Deasy, Joseph O; Ibbott, Geoffrey S; Vicic, Milos; White, R Allen; Followill, David S

2016-08-01

A dose calculation tool, which combines the accuracy of the dose planning method (DPM) Monte Carlo code and the versatility of a practical analytical multisource model, which was previously reported has been improved and validated for the Varian 6 and 10 MV linear accelerators (linacs). The calculation tool can be used to calculate doses in advanced clinical application studies. One shortcoming of current clinical trials that report dose from patient plans is the lack of a standardized dose calculation methodology. Because commercial treatment planning systems (TPSs) have their own dose calculation algorithms and the clinical trial participant who uses these systems is responsible for commissioning the beam model, variation exists in the reported calculated dose distributions. Today's modern linac is manufactured to tight specifications so that variability within a linac model is quite low. The expectation is that a single dose calculation tool for a specific linac model can be used to accurately recalculate dose from patient plans that have been submitted to the clinical trial community from any institution. The calculation tool would provide for a more meaningful outcome analysis. The analytical source model was described by a primary point source, a secondary extra-focal source, and a contaminant electron source. Off-axis energy softening and fluence effects were also included. The additions of hyperbolic functions have been incorporated into the model to correct for the changes in output and in electron contamination with field size. A multileaf collimator (MLC) model is included to facilitate phantom and patient dose calculations. An offset to the MLC leaf positions was used to correct for the rudimentary assumed primary point source. Dose calculations of the depth dose and profiles for field sizes 4 × 4 to 40 × 40 cm agree with measurement within 2% of the maximum dose or 2 mm distance to agreement (DTA) for 95% of the data points tested. The model was capable of predicting the depth of the maximum dose within 1 mm. Anthropomorphic phantom benchmark testing of modulated and patterned MLCs treatment plans showed agreement to measurement within 3% in target regions using thermoluminescent dosimeters (TLD). Using radiochromic film normalized to TLD, a gamma criteria of 3% of maximum dose and 2 mm DTA was applied with a pass rate of least 85% in the high dose, high gradient, and low dose regions. Finally, recalculations of patient plans using DPM showed good agreement relative to a commercial TPS when comparing dose volume histograms and 2D dose distributions. A unique analytical source model coupled to the dose planning method Monte Carlo dose calculation code has been modified and validated using basic beam data and anthropomorphic phantom measurement. While this tool can be applied in general use for a particular linac model, specifically it was developed to provide a singular methodology to independently assess treatment plan dose distributions from those clinical institutions participating in National Cancer Institute trials.

Safety and activity of temsirolimus and bevacizumab in patients with advanced renal cell carcinoma previously treated with tyrosine kinase inhibitors: a phase 2 consortium study.

PubMed

Merchan, Jaime R; Qin, Rui; Pitot, Henry; Picus, Joel; Liu, Glenn; Fitch, Tom; Maples, William J; Flynn, Patrick J; Fruth, Briant F; Erlichman, Charles

2015-03-01

Bevacizumab or temsirolimus regimens have clinical activity in the first-line treatment of advanced renal cell carcinoma (RCC). This phase I/II trial was conducted to determine the safety of combining both agents and its efficacy in RCC patients who progressed on at least one prior anti-VEGF receptor tyrosine kinase inhibitor (RTKI) agent. In the phase I portion, eligible patients were treated with temsirolimus (25 mg IV weekly) and escalating doses of IV bevacizumab (level 1 = 5 mg/kg; level 2 = 10 mg/kg) every other week. The primary endpoint for the phase II portion (RTKI resistant patients) was the 6-month progression-free rate. Secondary endpoints were response rate, toxicity evaluation, and PFS and OS. Maximum tolerated dose was not reached at the maximum dose administered in 12 phase I patients. Forty evaluable patients were treated with the phase II recommended dose (temsirolimus 25 mg IV weekly and bevacizumab 10 mg/kg IV every 2 weeks). The 6-month progression-free rate was 40 % (16/40 pts). Median PFS was 5.9 (4-7.8) months, and median OS was 20.6 (11.5-23.7) months. Partial response, stable disease, and progressive disease were seen in 23, 63, and 14 % of patients, respectively. Most common grade 3-4 AEs included fatigue (17.8 %), hypertriglyceridemia (11.1 %), stomatitis (8.9 %), proteinuria (8.9 %), abdominal pain (6.7 %), and anemia (6.7 %). Baseline levels of serum sFLT-1 and VEGF-A were inversely correlated with PFS and OS, respectively. Temsirolimus and bevacizumab is a feasible combination in patients with advanced RCC previously exposed to oral anti-VEGF agents. The safety and efficacy results warrant further confirmatory studies in this patient population.

On the use of volumetric-modulated arc therapy for single-fraction thoracic vertebral metastases stereotactic body radiosurgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pokhrel, Damodar, E-mail: damodar.pokhrel@uky.edu; Sood, Sumit; McClinton, Christopher

To retrospectively evaluate quality, efficiency, and delivery accuracy of volumetric-modulated arc therapy (VMAT) plans for single-fraction treatment of thoracic vertebral metastases using image-guided stereotactic body radiosurgery (SBRS) after RTOG 0631 dosimetric compliance criteria. After obtaining credentialing for MD Anderson spine phantom irradiation validation, 10 previously treated patients with thoracic vertebral metastases with noncoplanar hybrid arcs using 1 to 2 3D-conformal partial arcs plus 7 to 9 intensity-modulated radiation therapy beams were retrospectively re-optimized with VMAT using 3 full coplanar arcs. Tumors were located between T2 and T12. Contrast-enhanced T1/T2-weighted magnetic resonance images were coregistered with planning computed tomography and planningmore » target volumes (PTV) were between 14.4 and 230.1 cc (median = 38.0 cc). Prescription dose was 16 Gy in 1 fraction with 6 MV beams at Novalis-TX linear accelerator consisting of micro multileaf collimators. Each plan was assessed for target coverage using conformality index, the conformation number, the ratio of the volume receiving 50% of the prescription dose over PTV, R50%, homogeneity index (HI), and PTV-1600 coverage per RTOG 0631 requirements. Organs-at-risk doses were evaluated for maximum doses to spinal cord (D{sub 0.03} {sub cc}, D{sub 0.35} {sub cc}), partial spinal cord (D{sub 10%}), esophagus (D{sub 0.03} {sub cc} and D{sub 5} {sub cc}), heart (D{sub 0.03} {sub cc} and D{sub 15} {sub cc}), and lung (V{sub 5}, V{sub 10}, and maximum dose to 1000 cc of lung). Dose delivery efficiency and accuracy of each VMAT-SBRS plan were assessed using quality assurance (QA) plan on MapCHECK device. Total beam-on time was recorded during QA procedure, and a clinical gamma index (2%/2 mm and 3%/3 mm) was used to compare agreement between planned and measured doses. All 10 VMAT-SBRS plans met RTOG 0631 dosimetric requirements for PTV coverage. The plans demonstrated highly conformal and homogenous coverage of the vertebral PTV with mean HI, conformality index, conformation number, and R{sub 50%} values of 0.13 ± 0.03 (range: 0.09 to 0.18), 1.03 ± 0.04 (range: 0.98 to 1.09), 0.81 ± 0.06 (range: 0.72 to 0.89), and 4.2 ± 0.94 (range: 2.7 to 5.4), respectively. All 10 patients met protocol guidelines with maximum dose to spinal cord (average: 8.83 ± 1.9 Gy, range: 5.9 to 10.9 Gy); dose to 0.35 cc of spinal cord (average: 7.62 ± 1.7 Gy, range: 5.4 to 9.6 Gy); and dose to 10% of partial spinal cord (average 6.31 ± 1.5 Gy, range: 3.5 to 8.5 Gy) less than 14, 10, and 10 Gy, respectively. For all 10 patients, the maximum dose to esophagus (average: 9.41 ± 4.3 Gy, range: 1.5 to 14.9 Gy) and dose to 5 cc of esophagus (average: 7.43 ± 3.8 Gy, range: 1.1 to 11.8 Gy) were kept less than protocol requirements 16 Gy and 11.9 Gy, respectively. In a similar manner, all 10 patients met protocol compliance criteria with maximum dose to heart (average: 4.62 ± 3.5 Gy, range: 1.3 to 10.2 Gy) and dose to 15 cc of heart (average: 2.23 ± 1.8 Gy, range: 0.3 to 5.6 Gy) less than 22 and 16 Gy, respectively. The dose to the lung was retained much lower than protocol guidelines for all 10 patients. The total number of monitor units was, on average, 6919 ± 1187. The average beam-on time was 11.5 ± 2.0 minutes. The VMAT plans demonstrated dose delivery accuracy of 95.8 ± 0.7%, on average, for clinical gamma passing rate with 2%/2 mm criteria and 98.3 ± 0.8%, on average, with 3%/3 mm criteria. All VMAT-SBRS plans were considered clinically acceptable per RTOG 0631 dosimetric compliance criteria. VMAT planning provided highly conformal and homogenous dose distributions for the lower-dose vertebral PTV and the spinal cord as well as organs-at-risk such as esophagus, heart, and lung. Higher QA pass rates and shorter beam-on time suggest that VMAT-SBRS is a clinically feasible, fast, and effective treatment option for patients with thoracic vertebral metastases.« less

PCP METHODOLOGY FOR DETERMINING DOSE RATES FOR SMALL GRAM QUANTITIES IN SHIPPING PACKAGINGS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nathan, S.

The Small Gram Quantity (SGQ) concept is based on the understanding that small amounts of hazardous materials, in this case radioactive materials, are significantly less hazardous than large amounts of the same materials. This study describes a methodology designed to estimate an SGQ for several neutron and gamma emitting isotopes that can be shipped in a package compliant with 10 CFR Part 71 external radiation level limits regulations. These regulations require packaging for the shipment of radioactive materials perform, under both normal and accident conditions, the essential functions of material containment, subcriticality, and maintain external radiation levels within regulatory limits.more » 10 CFR 71.33(b)(1)(2)&(3) state radioactive and fissile materials must be identified and their maximum quantity, chemical and physical forms be included in an application. Furthermore, the U.S. Federal Regulations require application contain an evaluation demonstrating the package (i.e., the packaging and its contents) satisfies the external radiation standards for all packages (10 CFR 71.31(2), 71.35(a), & 71.47). By placing the contents in a He leak-tight containment vessel, and limiting the mass to ensure subcriticality, the first two essential functions are readily met. Some isotopes emit sufficiently strong photon radiation that small amounts of material can yield a large external dose rate. Quantifying of the dose rate for a proposed content is a challenging issue for the SGQ approach. It is essential to quantify external radiation levels from several common gamma and neutron sources that can be safely placed in a specific packaging, to ensure compliance with federal regulations. The Packaging Certification Program (PCP) Methodology for Determining Dose Rate for Small Gram Quantities in Shipping Packagings described in this report provides bounding mass limits for a set of proposed SGQ isotopes. Methodology calculations were performed to estimate external radiation levels for the 9977 shipping package using the MCNP radiation transport code to develop a set of response multipliers (Green's functions) for 'dose per particle' for each neutron and photon spectral group. The source spectrum for each isotope generated using the ORIGEN-S and RASTA computer codes was folded with the response multipliers to generate the dose rate per gram of each isotope in the 9977 shipping package and its associated shielded containers. The maximum amount of a single isotope that could be shipped within the regulatory limits contained in 10 CFR 71.47 for dose rate at the surface of the package is determined. If a package contains a mixture of isotopes, the acceptability for shipment can be determined by a sum of fractions approach. Furthermore, the results of this analysis can be easily extended to additional radioisotopes by simply evaluating the neutron and/or photon spectra of those isotopes and folding the spectral data with the Green's functions provided.« less

The maximum single dose of resistant maltodextrin that does not cause diarrhea in humans.

PubMed

Kishimoto, Yuka; Kanahori, Sumiko; Sakano, Katsuhisa; Ebihara, Shukuko

2013-01-01

The objective of the present study was to determine the maximum dose of resistant maltodextrin (Fibersol)-2, a non-viscous water-soluble dietary fiber), that does not induce transitory diarrhea. Ten healthy adult subjects (5 men and 5 women) ingested Fibersol-2 at increasing dose levels of 0.7, 0.8, 0.9, 1.0, and 1.1 g/kg body weight (bw). Each administration was separated from the previous dose by an interval of 1 wk. The highest dose level that did not cause diarrhea in any subject was regarded as the maximum non-effective level for a single dose. The results showed that no subject of either sex experienced diarrhea at dose levels of 0.7, 0.8, 0.9, or 1.0 g/kg bw. At the highest dose level of 1.1 g/kg bw, no female subject experienced diarrhea, whereas 1 male subject developed diarrhea with muddy stools 2 h after ingestion of the test substance. Consequently, the maximum non-effective level for a single dose of the resistant maltodextrin Fibersol-2 is 1.0 g/kg bw for men and >1.1 g/kg bw for women. Gastrointestinal symptoms were gurgling sounds in 4 subjects (7 events) and flatus in 5 subjects (9 events), although no association with dose level was observed. These symptoms were mild and transient and resolved without treatment.

Monte Carlo simulations of the secondary neutron ambient and effective dose equivalent rates from surface to suborbital altitudes and low Earth orbit

NASA Astrophysics Data System (ADS)

El-Jaby, Samy; Richardson, Richard B.

2015-07-01

Occupational exposures from ionizing radiation are currently regulated for airline travel (<20 km) and for missions to low-Earth orbit (∼300-400 km). Aircrew typically receive between 1 and 6 mSv of occupational dose annually, while aboard the International Space Station, the area radiation dose equivalent measured over just 168 days was 106 mSv at solar minimum conditions. It is anticipated that space tourism vehicles will reach suborbital altitudes of approximately 100 km and, therefore, the annual occupational dose to flight crew during repeated transits is expected to fall somewhere between those observed for aircrew and astronauts. Unfortunately, measurements of the radiation environment at the high altitudes reached by suborbital vehicles are sparse, and modelling efforts have been similarly limited. In this paper, preliminary MCNPX radiation transport code simulations are developed of the secondary neutron flux profile in air from surface altitudes up to low Earth orbit at solar minimum conditions and excluding the effects of spacecraft shielding. These secondary neutrons are produced by galactic cosmic radiation interacting with Earth's atmosphere and are among the sources of radiation that can pose a health risk. Associated estimates of the operational neutron ambient dose equivalent, used for radiation protection purposes, and the neutron effective dose equivalent that is typically used for estimates of stochastic health risks, are provided in air. Simulations show that the neutron radiation dose rates received at suborbital altitudes are comparable to those experienced by aircrew flying at 7 to 14 km. We also show that the total neutron dose rate tails off beyond the Pfotzer maximum on ascension from surface up to low Earth orbit.

Monte Carlo simulations of the secondary neutron ambient and effective dose equivalent rates from surface to suborbital altitudes and low Earth orbit.

PubMed

El-Jaby, Samy; Richardson, Richard B

2015-07-01

Occupational exposures from ionizing radiation are currently regulated for airline travel (<20 km) and for missions to low-Earth orbit (∼300-400 km). Aircrew typically receive between 1 and 6 mSv of occupational dose annually, while aboard the International Space Station, the area radiation dose equivalent measured over just 168 days was 106 mSv at solar minimum conditions. It is anticipated that space tourism vehicles will reach suborbital altitudes of approximately 100 km and, therefore, the annual occupational dose to flight crew during repeated transits is expected to fall somewhere between those observed for aircrew and astronauts. Unfortunately, measurements of the radiation environment at the high altitudes reached by suborbital vehicles are sparse, and modelling efforts have been similarly limited. In this paper, preliminary MCNPX radiation transport code simulations are developed of the secondary neutron flux profile in air from surface altitudes up to low Earth orbit at solar minimum conditions and excluding the effects of spacecraft shielding. These secondary neutrons are produced by galactic cosmic radiation interacting with Earth's atmosphere and are among the sources of radiation that can pose a health risk. Associated estimates of the operational neutron ambient dose equivalent, used for radiation protection purposes, and the neutron effective dose equivalent that is typically used for estimates of stochastic health risks, are provided in air. Simulations show that the neutron radiation dose rates received at suborbital altitudes are comparable to those experienced by aircrew flying at 7 to 14 km. We also show that the total neutron dose rate tails off beyond the Pfotzer maximum on ascension from surface up to low Earth orbit. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

A gradient of radioactive contamination in Dolon village near the SNTS and comparison of computed dose values with instrumental estimates for the 29 August, 1949 nuclear test.

PubMed

Stepanenko, Valeriy F; Hoshi, Masaharu; Dubasov, Yuriy V; Sakaguchi, Aya; Yamamoto, Masayoshi; Orlov, Mark Y; Bailiff, Ian K; Ivannikov, Alexander I; Skvortsov, Valeriy G; Iaskova, Elena K; Kryukova, Irina G; Zhumadilov, Kassym S; Endo, Satoru; Tanaka, Kenichi; Apsalikov, Kazbek N; Gusev, Boris I

2006-02-01

Spatial distributions of soil contamination by 137Cs (89 sampling points) and 239+240Pu (76 points) near and within Dolon village were analyzed. An essential exponential decrease of contamination was found in Dolon village: the distance of a half reduction in contamination is about 0.87-1.25 km (in a northwest-southeast direction from the supposed centerline of the radioactive trace). This fact is in agreement with the available exposure rate measurements near Dolon (September 1949 archive data): on the basis of a few measurements the pattern of the trace was estimated to comprise a narrow 2 km corridor of maximum exposure rate. To compare computed external doses in air with local dose estimates by retrospective luminescence dosimetry (RLD) the gradient of radioactive soil contamination within the village was accounted for. The computed dose associated with the central axis of the trace was found to be equal to 2260 mGy (calculations based on archive exposure rate data). Local doses near the RLD sampling points (southeast of the village) were calculated to be in the range 466-780 mGy (averaged value: 645+/-70 mGy), which is comparable with RLD data (averaged value 460+/-92 mGy with range 380-618 mGy). A comparison of the computed mean dose in the settlement with dose estimates by ESR tooth enamel dosimetry makes it possible to estimate the "upper level" of the "shielding and behavior" factor in dose reduction for inhabitants of Dolon village which was found to be 0.28+/-0.068.

SU-E-J-169: The Dosimetric and Temporal Effects of Respiratory-Gated Radiation Therapy in Lung Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rouabhi, O; Gross, B; Xia, J

2015-06-15

Purpose: To evaluate the dosimetric and temporal effects of high dose rate treatment mode for respiratory-gated radiation therapy in lung cancer patients. Methods: Treatment plans from five lung cancer patients (3 nongated (Group 1), 2 gated at 80EX-80IN (Group 2)) were retrospectively evaluated. The maximum tumor motions range from 6–12 mm. Using the same planning criteria, four new treatment plans, corresponding to four gating windows (20EX–20IN, 40EX–40IN, 60EX–60IN, and 80EX–80IN), were generated for each patient. Mean tumor dose (MTD), mean lung dose (MLD), and lung V20 were used to assess the dosimetric effects. A MATLAB algorithm was developed to computemore » treatment time by considering gantry rotation time, time to position collimator leaves, dose delivery time (scaled relative to the gating window), and communication overhead. Treatment delivery time for each plan was estimated using a 500 MU/min dose rate for the original plans and a 1500 MU/min dose rate for the gated plans. Results: Differences in MTD were less than 1Gy across plans for all five patients. MLD and lung V20 were on average reduced between −16.1% to −6.0% and −20.0% to −7.2%, respectively for non-gated plans when compared with the corresponding gated plans, and between − 5.8% to −4.2% and −7.0% to −5.4%, respectively for plans originally gated at 80EX–80IN when compared with the corresponding 20EX-20IN to 60EX– 60IN gated plans. Treatment delivery times of gated plans using high dose rate were reduced on average between −19.7% (−1.9min) to −27.2% (−2.7min) for originally non-gated plans and −15.6% (−0.9min) to −20.3% (−1.2min) for originally 80EX-80IN gated plans. Conclusion: Respiratory-gated radiation therapy in lung cancer patients can reduce lung toxicity, while maintaining tumor dose. Using a gated high-dose-rate treatment, delivery time comparable to non-gated normal-dose-rate treatment can be achieved. This research is supported by Siemens Medical Solutions USA, Inc.« less

Image quality evaluation and patient dose assessment of medical fluoroscopic X-ray systems: a national study.

PubMed

Economides, S; Hourdakis, C J; Kalivas, N; Kalathaki, M; Simantirakis, G; Tritakis, P; Manousaridis, G; Vogiatzi, S; Kipouros, P; Boziari, A; Kamenopoulou, V

2008-01-01

This study presents the results from a survey conducted by the Greek Atomic Energy Commission (GAEC), during the period 1998-2003, in 530 public and private owned fluoroscopic X-ray systems in Greece. Certain operational parameters for conventional and remote control systems were assessed, according to a quality control protocol developed by GAEC on the basis of the current literature. Public (91.5%) and private (81.5%) owned fluoroscopic units exhibit high-contrast resolution values over 1 lp mm(-1). Moreover, 88.5 and 87.1% of the fluoroscopic units installed in the public and private sector, respectively, present Maximum Patient Entrance Kerma Rate values lower than 100 mGy min(-1). Additionally, 68.3% of the units assessed were found to perform within the acceptance limits. Finally, the third quartile of the Entrance Surface Dose Rate distribution was estimated according to the Dose Reference Level definition and found equal to 35 mGy min(-1).

Formulation and Development of Metered Dose Inhalations of Salbutamol in Solution Form

PubMed Central

Khale, Anubha; Bajaj, Amrita

2011-01-01

In the present study attempts were made to prepare metered dose inhalation of salbutamol in solution form and compared it with the marketed metered dose inhalation in suspension form. Solution form of the drug was found better than marketed suspension formulation with respect to homogeneity and content uniformity. Propellant blend P-11 and P-12 in the proportion 30:70 was selected as it gave optimum vapour pressure. Surfactant oleic acid in concentration 10 mg per can was selected as it gave best results with clarity, spray pattern, vapour pressure, content per spray and rate of evaporation. Ethyl alcohol 2 ml per can was used as a cosolvent to give a clear solution, optimum vapour pressure, maximum content per spray and fair rate of evaporation. The selected formulation was subjected to the physico-chemical evaluation tests as per the standard pharmacopoeial procedures and the characteristics of the formulations were further compared with a conventional marketed formulation. In vitro study reveled the net respirable fraction was better than marketed preparation. PMID:22923867

TU-AB-201-06: Evaluation of Electromagnetically Guided High- Dose Rate Brachytherapy for Ablative Treatment of Lung Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pinkham, D.W.; Shultz, D.; Loo, B.W.

Purpose: The advent of electromagnetic navigation bronchoscopy has enabled minimally invasive access to peripheral lung tumors previously inaccessible by optical bronchoscopes. As an adjunct to Stereotactic Ablative Radiosurgery (SABR), implantation of HDR catheters can provide focal treatments for multiple metastases and sites of retreatments. The authors evaluate a procedure to deliver ablative doses via Electromagnetically-Guided HDR (EMG-HDR) to lung metastases, quantify the resulting dosimetry, and assess its role in the comprehensive treatment of lung cancer. Methods: A retrospective study was conducted on ten patients, who, from 2009 to 2011, received a hypo-fractionated SABR regimen with 6MV VMAT to lesions inmore » various lobes ranging from 1.5 to 20 cc in volume. A CT visible pathway was delineated for EM guided placement of an HDR applicator (catheter) and dwell times were optimized to ensure at least 98% prescription dose coverage of the GTV. Normal tissue doses were calculated using inhomogeneity corrections via a grid-based Boltzmann solver (Acuros-BV-1.5.0). Results: With EMG-HDR, an average of 83% (+/−9% standard deviation) of each patient’s GTV received over 200% of the prescription dose, as compared to SABR where the patients received an average maximum dose of 125% (+/−5%). EMG-HDR enabled a 59% (+/−12%) decrease in the aorta maximum dose, a 63% (+/−26%) decrease in the spinal cord max dose, and 57% (+/−23%) and 70% (+/−17%) decreases in the volume of the body receiving over 50% and 25% of the prescription dose, respectively. Conclusion: EMG-HDR enables delivery of higher ablative doses to the GTV, while concurrently reducing surrounding normal tissue doses. The single catheter approach shown here is limited to targets smaller than 20 cc. As such, the technique enables ablation of small lesions and a potentially safe and effective retreatment option in situations where external beam utility is limited by normal tissue constraints.« less

Prospective, open, multicentre Phase I/II trial to assess safety and efficacy of neoadjuvant radiochemotherapy with docetaxel and cisplatin for esophageal carcinoma.

PubMed

Ma, Hong-Bing; Di, Zheng-Li; Wen, Jiao; Ke, Yue; Sun, Xiaodong; Ren, Juan

2015-02-01

Esophageal squamous cell carcinoma is increasingly treated with trimodality therapy. The objective of this Phase I/II clinical study is to assess the efficacy and safety of neoadjuvant radiochemotherapy with docetaxel and cisplatin and radiotherapy in patients with esophagectomy for locally advanced squamous cell carcinoma of the esophagus with neoadjuvant chemoradiotherapy. Patients with esophageal squamous cell carcinoma received radiochemotherapy (50 Gy/25 fractions during Weeks 1-5) using a three-dimensional conformal radiation therapy or intensity-modulated radiation therapy technique together with weekly docetaxel (20 mg/m(2) at dose levels 1 and 2, 25 mg/m(2) at dose level 3 on Weeks 1-5) and cisplatin (30 mg/m(2) at dose level 1, 40 mg/m(2) at dose levels 2 and 3 on Weeks 1-5) from January 2009 to December 2011. The dose-limiting toxicities and maximum tolerated dose were the primary endpoints and overall response rate and progression-free survival were the secondary endpoints. Over this timeframe, a total of 49 patients completed trimodality therapy. Thirteen patients were treated at dose level 1, 21 patients at dose level 2 and 15 patients at dose level 3.The maximum tolerated dose for docetaxel was 20 mg/m(2) and cisplatin 40 mg/m(2). The complete response or partial response was observed in 26.5% (13/49) of patients. Thirty-four patients (69.4%) were treated with neoadjuvant radiochemotherapy followed by surgical resection. The median progression-free survival and median overall survival for all patients (n = 49) were 8 and 17.2 months, respectively. The median overall survival was 27.5 months for patients treated at dose level 2. Neoadjuvant radiochemotherapy with docetaxel 20 mg/m(2) and cisplatin 40 mg/m(2) was effective and tolerable induction regimen in patients with esophageal tumors. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Estimation of eye lens doses received by pediatric interventional cardiologists.

PubMed

Alejo, L; Koren, C; Ferrer, C; Corredoira, E; Serrada, A

2015-09-01

Maximum Hp(0.07) dose to the eye lens received in a year by the pediatric interventional cardiologists has been estimated. Optically stimulated luminescence dosimeters were placed on the eyes of an anthropomorphic phantom, whose position in the room simulates the most common irradiation conditions. Maximum workload was considered with data collected from procedures performed in the Hospital. None of the maximum values obtained exceed the dose limit of 20 mSv recommended by ICRP. Copyright © 2015 Elsevier Ltd. All rights reserved.

Knowledge of appropriate acetaminophen doses and potential toxicities in an adult clinic population.

PubMed

Stumpf, Janice L; Skyles, Amy J; Alaniz, Cesar; Erickson, Steven R

2007-01-01

To evaluate the knowledge of appropriate doses and potential toxicities of acetaminophen and assess the ability to recognize products containing acetaminophen in an adult outpatient setting. Cross-sectional, prospective study. University adult general internal medicine (AGIM) clinic. 104 adult patients presenting to the clinic over consecutive weekdays in December 2003. Three-page, written questionnaire. Ability of patients to identify maximum daily doses and potential toxicities of acetaminophen and recognize products that contain acetaminophen. A large percentage of participants (68.3%) reported pain on a daily or weekly basis, and 78.9% reported use of acetaminophen in the past 6 months. Only 2 patients correctly identified the maximum daily dose of regular acetaminophen, and just 3 correctly identified the maximum dose of extra-strength acetaminophen. Furthermore, 28 patients were unsure of the maximum dose of either product. Approximately 63% of participants either had not received or were unsure whether information on the possible danger of high doses of acetaminophen had been previously provided to them. When asked to identify potential problems associated with high doses of acetaminophen, 43.3% of patients noted the liver would be affected. The majority of the patients (71.2%) recognized Tylenol as containing acetaminophen, but fewer than 15% correctly identified Vicodin, Darvocet, Tylox, Percocet, and Lorcet as containing acetaminophen. Although nearly 80% of this AGIM population reported recent acetaminophen use, their knowledge of the maximum daily acetaminophen doses and potential toxicities associated with higher doses was poor and appeared to be independent of education level, age, and race. This indicates a need for educational efforts to all patients receiving acetaminophen-containing products, especially since the ability to recognize multi-ingredient products containing acetaminophen was likewise poor.

Factors Influencing the Cardiovascular Response to Subanesthetic Ketamine: A Randomized, Placebo-Controlled Trial

PubMed Central

Li, Shijia; Lord, Anton; Colic, Lejla; Krause, Anna Linda; Batra, Anil; Kretzschmar, Moritz A; Sweeney-Reed, Catherine M; Behnisch, Gusalija; Schott, Björn H; Walter, Martin

2017-01-01

Abstract Background The increasing use of ketamine as a potential rapid-onset antidepressant necessitates a better understanding of its effects on blood pressure and heart rate, well-known side effects at higher doses. For the subanesthetic dose used for depression, potential predictors of these cardiovascular effects are important factors influencing clinical decisions. Since ketamine influences the sympathetic nervous system, we investigated the impact of autonomic nervous system-related factors on the cardiovascular response: a genetic polymorphism in the norepinephrine transporter and gender effects. Methods Blood pressure and heart rate were monitored during and following administration of a subanesthetic dose of ketamine or placebo in 68 healthy participants (mean age 26.04 ±5.562 years) in a double-blind, randomized, controlled, parallel-design trial. The influences of baseline blood pressure/heart rate, gender, and of a polymorphism in the norepinephrine transporter gene (NET SLC6A2, rs28386840 [A-3081T]) on blood pressure and heart rate changes were investigated. To quantify changes in blood pressure and heart rate, we calculated the maximum change from baseline (ΔMAX) and the time until maximum change (TΔMAX). Results Systolic and diastolic blood pressure as well as heart rate increased significantly upon ketamine administration, but without reaching hypertensive levels. During administration, the systolic blood pressure at baseline (TP0Sys) correlated negatively with the time to achieve maximal systolic blood pressure (TΔMAXSys, P<.001). Furthermore, women showed higher maximal diastolic blood pressure change (ΔMAXDia, P<.001) and reached this peak earlier than men (TΔMAXDia, P=.017) at administration. NET rs28386840 [T] carriers reached their maximal systolic blood pressure during ketamine administration significantly earlier than [A] homozygous (TΔMAXSys, P=.030). In a combined regression model, both genetic polymorphism and TP0Sys were significant predictors of TΔMAXSys (P<.0005). Conclusions Subanesthetic ketamine increased both blood pressure and heart rate without causing hypertensive events. Furthermore, we identified gender and NET rs28386840 genotype as factors that predict increased cardiovascular sequelae of ketamine administration in our young, healthy study population providing a potential basis for establishing monitoring guidelines. PMID:29099972

Randomized Noninferiority Trial of Reduced High-Dose Volume Versus Standard Volume Radiation Therapy for Muscle-Invasive Bladder Cancer: Results of the BC2001 Trial (CRUK/01/004)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huddart, Robert A., E-mail: robert.huddart@icr.ac.uk; Hall, Emma; Hussain, Syed A.

2013-10-01

Purpose: To test whether reducing radiation dose to uninvolved bladder while maintaining dose to the tumor would reduce side effects without impairing local control in the treatment of muscle-invasive bladder cancer. Methods and Materials: In this phase III multicenter trial, 219 patients were randomized to standard whole-bladder radiation therapy (sRT) or reduced high-dose volume radiation therapy (RHDVRT) that aimed to deliver full radiation dose to the tumor and 80% of maximum dose to the uninvolved bladder. Participants were also randomly assigned to receive radiation therapy alone or radiation therapy plus chemotherapy in a partial 2 × 2 factorial design. Themore » primary endpoints for the radiation therapy volume comparison were late toxicity and time to locoregional recurrence (with a noninferiority margin of 10% at 2 years). Results: Overall incidence of late toxicity was less than predicted, with a cumulative 2-year Radiation Therapy Oncology Group grade 3/4 toxicity rate of 13% (95% confidence interval 8%, 20%) and no statistically significant differences between groups. The difference in 2-year locoregional recurrence free rate (RHDVRT − sRT) was 6.4% (95% confidence interval −7.3%, 16.8%) under an intention to treat analysis and 2.6% (−12.8%, 14.6%) in the “per-protocol” population. Conclusions: In this study RHDVRT did not result in a statistically significant reduction in late side effects compared with sRT, and noninferiority of locoregional control could not be concluded formally. However, overall low rates of clinically significant toxicity combined with low rates of invasive bladder cancer relapse confirm that (chemo)radiation therapy is a valid option for the treatment of muscle-invasive bladder cancer.« less

Density Dependence and Growth Rate: Evolutionary Effects on Resistance Development to Bt (Bacillus thuringiensis).

PubMed

Martinez, Jeannette C; Caprio, Michael A; Friedenberg, Nicholas A

2018-02-09

It has long been recognized that pest population dynamics can affect the durability of a pesticide, but dose remains the primary component of insect resistance management (IRM). For transgenic pesticidal traits such as Bt (Bacillus thuringiensis Berliner (Bacillales: Bacillaceae)), dose (measured as the mortality of susceptibles caused by a toxin) is a relatively fixed characteristic and often falls below the standard definition of high dose. Hence, it is important to understand how pest population dynamics modify durability and what targets they present for IRM. We used a deterministic model of a generic arthropod pest to examine how timing and strength of density dependence interacted with population growth rate and Bt mortality to affect time to resistance. As in previous studies, durability typically reached a minimum at intermediate doses. However, high population growth rates could eliminate benefits of high dose. The timing of density dependence had a more subtle effect. If density dependence operated simultaneously with Bt mortality, durability was insensitive to its strengths. However, if density dependence was driven by postselection densities, decreasing its strength could increase durability. The strength of density dependence could affect durability of both single traits and pyramids, but its influence depended on the timing of density dependence and size of the refuge. Our findings suggest the utility of a broader definition of high dose, one that incorporates population-dynamic context. That maximum growth rates and timing and strength of interactions causing density dependent mortality can all affect durability, also highlights the need for ecologically integrated approaches to IRM research. © The Author(s) 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Single toxin dose-response models revisited

DOE Office of Scientific and Technical Information (OSTI.GOV)

Demidenko, Eugene, E-mail: eugened@dartmouth.edu

The goal of this paper is to offer a rigorous analysis of the sigmoid shape single toxin dose-response relationship. The toxin efficacy function is introduced and four special points, including maximum toxin efficacy and inflection points, on the dose-response curve are defined. The special points define three phases of the toxin effect on mortality: (1) toxin concentrations smaller than the first inflection point or (2) larger then the second inflection point imply low mortality rate, and (3) concentrations between the first and the second inflection points imply high mortality rate. Probabilistic interpretation and mathematical analysis for each of the fourmore » models, Hill, logit, probit, and Weibull is provided. Two general model extensions are introduced: (1) the multi-target hit model that accounts for the existence of several vital receptors affected by the toxin, and (2) model with a nonzero mortality at zero concentration to account for natural mortality. Special attention is given to statistical estimation in the framework of the generalized linear model with the binomial dependent variable as the mortality count in each experiment, contrary to the widespread nonlinear regression treating the mortality rate as continuous variable. The models are illustrated using standard EPA Daphnia acute (48 h) toxicity tests with mortality as a function of NiCl or CuSO{sub 4} toxin. - Highlights: • The paper offers a rigorous study of a sigmoid dose-response relationship. • The concentration with highest mortality rate is rigorously defined. • A table with four special points for five morality curves is presented. • Two new sigmoid dose-response models have been introduced. • The generalized linear model is advocated for estimation of sigmoid dose-response relationship.« less

Surface dose measurements for highly oblique electron beams.

PubMed

Ostwald, P M; Kron, T

1996-08-01

Clinical applications of electrons may involve oblique incidence of beams, and although dose variations for angles up to 60 degrees from normal incidence are well documented, no results are available for highly oblique beams. Surface dose measurements in highly oblique beams were made using parallel-plate ion chambers and both standard LiF:Mg, Ti and carbon-loaded LiF Thermoluminescent Dosimeters (TLD). Obliquity factors (OBF) or surface dose at an oblique angle divided by the surface dose at perpendicular incidence, were obtained for electron energies between 4 and 20 MeV. Measurements were performed on a flat solid water phantom without a collimator at 100 cm SSD. Comparisons were also made to collimated beams. The OBFs of surface doses plotted against the angle of incidence increased to a maximum dose followed by a rapid dropoff in dose. The increase in OBF was more rapid for higher energies. The maximum OBF occurred at larger angles for higher-energy beams and ranged from 73 degrees for 4 MeV to 84 degrees for 20 MeV. At the dose maximum, OBFs were between 130% and 160% of direct beam doses, yielding surface doses of up to 150% of Dmax for the 20 MeV beam. At 2 mm depth the dose ratio was found to increase initially with angle and then decrease as Dmax moved closer to the surface. A higher maximum dose was measured at 2 mm depth than at the surface. A comparison of ion chamber types showed that a chamber with a small electrode spacing and large guard ring is required for oblique dose measurement. A semiempirical equation was used to model the dose increase at the surface with different energy electron beams.

Single i.v. ketamine augmentation of newly initiated escitalopram for major depression: results from a randomized, placebo-controlled 4-week study.

PubMed

Hu, Y-D; Xiang, Y-T; Fang, J-X; Zu, S; Sha, S; Shi, H; Ungvari, G S; Correll, C U; Chiu, H F K; Xue, Y; Tian, T-F; Wu, A-S; Ma, X; Wang, G

2016-02-01

While oral antidepressants reach efficacy after weeks, single-dose intravenous (i.v.) ketamine has rapid, yet time-limited antidepressant effects. We aimed to determine the efficacy and safety of single-dose i.v. ketamine augmentation of escitalopram in major depressive disorder (MDD). Thirty outpatients with severe MDD (17-item Hamilton Rating Scale for Depression total score ⩾ 24) were randomized to 4 weeks double-blind treatment with escitalopram 10 mg/day+single-dose i.v. ketamine (0.5 mg/kg over 40 min) or escitalopram 10 mg/day + placebo (0.9% i.v. saline). Depressive symptoms were measured using the Montgomery-Asberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR). Suicidal ideation was evaluated with the QIDS-SR item 12. Adverse psychopathological effects were measured with the Brief Psychiatric Rating Scale (BPRS)-positive symptoms, Young Mania Rating Scale (YMRS) and Clinician Administered Dissociative States Scale (CADSS). Patients were assessed at baseline, 1, 2, 4, 24 and 72 h and 7, 14, 21 and 28 days. Time to response (⩾ 50% MADRS score reduction) was the primary outcome. By 4 weeks, more escitalopram + ketamine-treated than escitalopram + placebo-treated patients responded (92.3% v. 57.1%, p = 0.04) and remitted (76.9% v. 14.3%, p = 0.001), with significantly shorter time to response [hazard ratio (HR) 0.04, 95% confidence interval (CI) 0.01-0.22, p < 0.001] and remission (HR 0.11, 95% CI 0.02-0.63, p = 0.01). Compared to escitalopram + placebo, escitalopram + ketamine was associated with significantly lower MADRS scores from 2 h to 2 weeks [(peak = 3 days-2 weeks; effect size (ES) = 1.08-1.18)], QIDS-SR scores from 2 h to 2 weeks (maximum ES = 1.27), and QIDS-SR suicidality from 2 to 72 h (maximum ES = 2.24). Only YMRS scores increased significantly with ketamine augmentation (1 and 2 h), without significant BPRS or CADSS elevation. Single-dose i.v. ketamine augmentation of escitalopram was safe and effective in severe MDD, holding promise for speeding up early oral antidepressant efficacy.

Uncertainties in estimating heart doses from 2D-tangential breast cancer radiotherapy.

PubMed

Lorenzen, Ebbe L; Brink, Carsten; Taylor, Carolyn W; Darby, Sarah C; Ewertz, Marianne

2016-04-01

We evaluated the accuracy of three methods of estimating radiation dose to the heart from two-dimensional tangential radiotherapy for breast cancer, as used in Denmark during 1982-2002. Three tangential radiotherapy regimens were reconstructed using CT-based planning scans for 40 patients with left-sided and 10 with right-sided breast cancer. Setup errors and organ motion were simulated using estimated uncertainties. For left-sided patients, mean heart dose was related to maximum heart distance in the medial field. For left-sided breast cancer, mean heart dose estimated from individual CT-scans varied from <1Gy to >8Gy, and maximum dose from 5 to 50Gy for all three regimens, so that estimates based only on regimen had substantial uncertainty. When maximum heart distance was taken into account, the uncertainty was reduced and was comparable to the uncertainty of estimates based on individual CT-scans. For right-sided breast cancer patients, mean heart dose based on individual CT-scans was always <1Gy and maximum dose always <5Gy for all three regimens. The use of stored individual simulator films provides a method for estimating heart doses in left-tangential radiotherapy for breast cancer that is almost as accurate as estimates based on individual CT-scans. Copyright © 2016. Published by Elsevier Ireland Ltd.

Dosimetric impact of applicator displacement during high dose rate (HDR) Cobalt-60 brachytherapy for cervical cancer: A planning study

NASA Astrophysics Data System (ADS)

Yong, J. S.; Ung, N. M.; Jamalludin, Z.; Malik, R. A.; Wong, J. H. D.; Liew, Y. M.; Ng, K. H.

2016-02-01

We investigated the dosimetric impact of applicator displacement on dose specification during high dose rate (HDR) Cobalt-60 (Co-60) brachytherapy for cervical cancer through a planning study. Eighteen randomly selected HDR full insertion plans were restrospectively studied. The tandem and ovoids were virtually shifted translationally and rotationally in the x-, y- and z-axis directions on the treatment planning system. Doses to reference points and volumes of interest in the plans with shifted applicators were compared with the original plans. The impact of dose displacement on 2D (point-based) and 3D (volume-based) treatment planning techniques was also assessed. A ±2 mm translational y-axis applicator shift and ±4° rotational x-axis applicator shift resulted in dosimetric changes of more than 5% to organs at risk (OAR) reference points. Changes to the maximum doses to 2 cc of the organ (D2cc) in 3D planning were statistically significant and higher than the reference points in 2D planning for both the rectum and bladder (p<0.05). Rectal D2cc was observed to be the most sensitive to applicator displacement among all dose metrics. Applicator displacement that is greater than ±2 mm translational y-axis and ±4° rotational x-axis resulted in significant dose changes to the OAR. Thus, steps must be taken to minimize the possibility of applicator displacement during brachytherapy.

HADOC: a computer code for calculation of external and inhalation doses from acute radionuclide releases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Strenge, D.L.; Peloquin, R.A.

The computer code HADOC (Hanford Acute Dose Calculations) is described and instructions for its use are presented. The code calculates external dose from air submersion and inhalation doses following acute radionuclide releases. Atmospheric dispersion is calculated using the Hanford model with options to determine maximum conditions. Building wake effects and terrain variation may also be considered. Doses are calculated using dose conversion factor supplied in a data library. Doses are reported for one and fifty year dose commitment periods for the maximum individual and the regional population (within 50 miles). The fractional contribution to dose by radionuclide and exposure modemore » are also printed if requested.« less

Comparison of two methods for minimizing the effect of delayed charge on the dose delivered with a synchrotron based discrete spot scanning proton beam.

PubMed

Whitaker, Thomas J; Beltran, Chris; Tryggestad, Erik; Bues, Martin; Kruse, Jon J; Remmes, Nicholas B; Tasson, Alexandria; Herman, Michael G

2014-08-01

Delayed charge is a small amount of charge that is delivered to the patient after the planned irradiation is halted, which may degrade the quality of the treatment by delivering unwarranted dose to the patient. This study compares two methods for minimizing the effect of delayed charge on the dose delivered with a synchrotron based discrete spot scanning proton beam. The delivery of several treatment plans was simulated by applying a normally distributed value of delayed charge, with a mean of 0.001(SD 0.00025) MU, to each spot. Two correction methods were used to account for the delayed charge. Method one (CM1), which is in active clinical use, accounts for the delayed charge by adjusting the MU of the current spot based on the cumulative MU. Method two (CM2) in addition reduces the planned MU by a predicted value. Every fraction of a treatment was simulated using each method and then recomputed in the treatment planning system. The dose difference between the original plan and the sum of the simulated fractions was evaluated. Both methods were tested in a water phantom with a single beam and simple target geometry. Two separate phantom tests were performed. In one test the dose per fraction was varied from 0.5 to 2 Gy using 25 fractions per plan. In the other test the number fractions were varied from 1 to 25, using 2 Gy per fraction. Three patient plans were used to determine the effect of delayed charge on the delivered dose under realistic clinical conditions. The order of spot delivery using CM1 was investigated by randomly selecting the starting spot for each layer, and by alternating per layer the starting spot from first to last. Only discrete spot scanning was considered in this study. Using the phantom setup and varying the dose per fraction, the maximum dose difference for each plan of 25 fractions was 0.37-0.39 Gy and 0.03-0.05 Gy for CM1 and CM2, respectively. While varying the total number of fractions, the maximum dose difference increased at a rate of 0.015 Gy and 0.0018 Gy per fraction for CM1 and CM2, respectively. For CM1, the largest dose difference was found at the location of the first spot in each energy layer, whereas for CM2 the difference in dose was small and showed no dependence on location. For CM1, all of the fields in the patient plans had an area where their excess dose overlapped. No such correlation was found when using CM2. Randomly selecting the starting spot reduces the maximum dose difference from 0.708 to 0.15 Gy. Alternating between first and last spot reduces the maximum dose difference from 0.708 to 0.37 Gy. In the patient plans the excess dose scaled linearly at 0.014 Gy per field per fraction for CM1 and standard delivery order. The predictive model CM2 is superior to a cumulative irradiation model CM1 for minimizing the effects of delayed charge, particularly when considering maximal dose discrepancies and the potential for unplanned hot-spots. This study shows that the dose discrepancy potentially scales at 0.014 Gy per field per fraction for CM1.

Carbon Ion Radiation Therapy With Concurrent Gemcitabine for Patients With Locally Advanced Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shinoto, Makoto, E-mail: shinoto@saga-himat.jp; Ion Beam Therapy Center, SAGA HIMAT Foundation, Tosu; Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka

Purpose: To determine, in the setting of locally advanced pancreatic cancer, the maximum tolerated dose of carbon ion radiation therapy (C-ion RT) and gemcitabine dose delivered concurrently and to estimate local effect and survival. Methods and Materials: Eligibility included pathologic confirmation of pancreatic invasive ductal carcinomas and radiographically unresectable disease without metastasis. Concurrent gemcitabine was administered on days 1, 8, and 15, and the dose levels were escalated from 400 to 1000 mg/m{sup 2} under the starting dose level (43.2 GyE) of C-ion RT. The dose levels of C-ion RT were escalated from 43.2 to 55.2 GyE at 12 fractions undermore » the fixed recommended gemcitabine dose determined. Results: Seventy-six patients were enrolled. Among the 72 treated patients, dose-limiting toxicity was observed in 3 patients: grade 3 infection in 1 patient and grade 4 neutropenia in 2 patients. Only 1 patient experienced a late grade 3 gastric ulcer and bleeding 10 months after C-ion RT. The recommended dose of gemcitabine with C-ion RT was found to be 1000 mg/m{sup 2}. The dose of C-ion RT with the full dose of gemcitabine (1000 mg/m{sup 2}) was safely increased to 55.2 GyE. The freedom from local progression rate was 83% at 2 years using the Response Evaluation Criteria in Solid Tumors. The 2-year overall survival rates in all patients and in the high-dose group with stage III (≥45.6 GyE) were 35% and 48%, respectively. Conclusions: Carbon ion RT with concurrent full-dose gemcitabine was well tolerated and effective in patients with unresectable locally advanced pancreatic cancer.« less

Dose optimization of contrast-enhanced carotid MR angiography.

PubMed

Unterweger, M; Froehlich, J M; Kubik-Huch, R A; Seifert, B; Birrer, M; Huber, T; Otto, R

2005-09-01

The purpose of this work was to compare the diagnostic performance of a single-contrast or a double-contrast dose of carotid contrast-enhanced MR angiography (MRA). One-hundred nineteen patients (mean age 65+/-14.4 years) underwent carotid contrast-enhanced MRA with a standardized protocol (repetition time/echo 3.73 ms/1.38 ms, flip-angle 25 degrees, acquisition-time 19 s, voxel size 1.2 x 1.2 x 0.9 mm3) on a 1.5-T scanner (Sonata, Siemens-Medical-Systems) using a neck phased-array coil. Contrast agent was administered intravenously at a rate of 3.0 ml/s, either as a single dose (n=57; 0.1 mmol/kg body weight) or as a double dose (n=62; 0.2 mmol/kg body weight) of meglumine gadoterate (0.5 M/l), followed by 30 ml saline. Qualitative image analysis was performed on maximum intensity projections using a five-point scale. Signal intensities were measured at three different vascular levels on both sides to assess the contrast-to-noise ratios (CNRs). Image quality was rated as good or excellent in all cases. A double dose did not influence the efficacy of carotid enhancement (CNR single dose 69.12+/-19.8; CNR double dose 70.01+/-20.7; p = 0.81) compared with a single dose. In both dose groups the mean CNRs were inversely related to bodyweight, despite adjusted contrast volumes (p=0.0005). Double-dose contrast-enhanced carotid MRA is not superior to single-dose MRA, as overall diagnostic performance and quantitative contrast enhancement are equal. Being more cost-efficient, a single-dose administration of contrast agent is recommended for MRA of the carotid arteries.

Effects of radioactive hot particles on pig skin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaurin, D.G.; Baum, J.W.; Schaefer, C.W.

1997-06-01

The purpose of these studies was to determine the incidence and severity of lesions resulting from very localized deposition of dose to skin from small (< 0.5 mm) discrete radioactive particles as produced in the work environments of nuclear reactors. Hanford mini-pigs were exposed, both on a slightly off the skin, to localized replicate doses from 0.31 to 64 Gy (averaged over 1 cm{sup 2} at 70 {mu}m depth unless noted otherwise) using Sc-46, Yb-175, Tm-170, and fissioned UC{sub 2} isotopes having maximum beta-particle energies from about 0.3 to 3 MeV. Erythema and scabs (indicating ulceration) were scored for upmore » to 71 days post-irradiation. The responses followed normal cumulative probability distributions, and therefore, no true threshold could be defined. Hence, 10 and 50% scab incidence rates were deduced using probit analyses. The lowest dose which produced 10% incidence was about 1 Gy for Yb-175 (0.5 MeV maximum energy) beta particle exposures, and about 3 to 9 Gy for other isotopes. The histopathology of lesions was determined at several doses. Single exposures to doses as large as 1,790 Gy were also given, and results were observed for up to 144 days post-exposure. Severity of detriment was estimated by analyzing the results in terms of lesion diameter, persistence, and infection. Over 1,100 sites were exposed. Only two exposed sites became infected after doses near 5000 Gy; the lesions healed quickly on treatment. 105 refs., 145 figs., 47 tabs.« less

Thyroid ultrasound abnormalities in persons exposed during childhood to 131I from the Hanford nuclear site.

PubMed

Kopecky, Kenneth J; Onstad, Lynn; Hamilton, Thomas E; Davis, Scott

2005-06-01

Approximately 740,000 Ci of 131I were released into the atmosphere from the Hanford Nuclear Site in Washington State during 1944-1957. The Hanford Thyroid Disease Study (HTDS), conducted to determine if thyroid disease is increased among persons exposed as children to that 131I, also investigated whether thyroid ultrasound (US) abnormalities might be increased. The HTDS cohort (n = 5199) was selected from 1940-1946 births to mothers with usual residence in seven Washington counties. Of these, 4350 were located alive, 3447 attended HTDS clinics (1992-1997), and 3440 (1747 females) had evaluable clinical results and sufficient data to characterize their Hanford 131I exposures. US abnormalities were observed in 55.5% of women and 37.4% of men. Thyroid radiation doses from Hanford 131I, which could be estimated for 3191 evaluable participants, ranged from 0.0029 to 2823 mGy (mean, 174 mGy). Estimated dose was not significantly associated with the prevalence of any US abnormality (p = 0.21), US nodules with maximum dimension 5 mm or more (p = 0.64), or average number of US nodules per person (p = 0.80 for nodules with maximum dimension 5 mm or more). These results remained unchanged after accounting for factors that might confound or modify dose-response relationships and for uncertainty of the dose estimates. This study does not support the hypothesis that 131I exposure at Hanford's dose levels and dose rates during infancy and childhood increases the prevalence of adult thyroid US abnormalities.

Volumetric-modulated Arc Therapy Lung Stereotactic Body Radiation Therapy Dosimetric Quality Assurance: A Comparison between Radiochromic Film and Chamber Array.

PubMed

Colodro, Juan Fernando Mata; Berná, Alfredo Serna; Puchades, Vicente Puchades; Amores, David Ramos; Baños, Miguel Alcaraz

2017-01-01

The aim of this work is to verify the use of radiochromic film in the quality assurance (QA) of volumetric-modulated arc therapy (VMAT) lung stereotactic body radiation therapy (SBRT) plans and compare the results with those obtained using an ion chamber array. QA was performed for 14 plans using a two-dimensional-array seven29 and EBT3 film. Dose values per session ranged between 7.5 Gy and 18 Gy. The multichannel method was used to obtain a dose map for film. The results obtained were compared with treatment planning system calculated profiles through gamma analysis. Passing criteria were 3%/3 mm, 2%/2 mm and 3%/1.5 mm with maximum and local dose (LD) normalization. Mean gamma passing rate (GPR) (percentage of points presenting a gamma function value of <1) was obtained and compared. Calibration curves were obtained for each color channel within the dose range 0-16 Gy. Mean GPR values for film were >98.9% for all criteria when normalizing per maximum dose. When using LD, normalization was >92.7%. GPR values for the array were lower for all criteria; this difference being statistically significant when normalizing at LD, reaching 12% for the 3%/1.5 mm criterion. Both detectors provide satisfactory results for the QA of plans for VMAT lung SBRT. The film provided greater mean GPR values, afforded greater spatial resolution and was more efficient overall.

Volumetric-modulated Arc Therapy Lung Stereotactic Body Radiation Therapy Dosimetric Quality Assurance: A Comparison between Radiochromic Film and Chamber Array

PubMed Central

Colodro, Juan Fernando Mata; Berná, Alfredo Serna; Puchades, Vicente Puchades; Amores, David Ramos; Baños, Miguel Alcaraz

2017-01-01

Introduction: The aim of this work is to verify the use of radiochromic film in the quality assurance (QA) of volumetric-modulated arc therapy (VMAT) lung stereotactic body radiation therapy (SBRT) plans and compare the results with those obtained using an ion chamber array. Materials and Methods: QA was performed for 14 plans using a two-dimensional-array seven29 and EBT3 film. Dose values per session ranged between 7.5 Gy and 18 Gy. The multichannel method was used to obtain a dose map for film. Results: The results obtained were compared with treatment planning system calculated profiles through gamma analysis. Passing criteria were 3%/3 mm, 2%/2 mm and 3%/1.5 mm with maximum and local dose (LD) normalization. Mean gamma passing rate (GPR) (percentage of points presenting a gamma function value of <1) was obtained and compared. Calibration curves were obtained for each color channel within the dose range 0–16 Gy. Mean GPR values for film were >98.9% for all criteria when normalizing per maximum dose. When using LD, normalization was >92.7%. GPR values for the array were lower for all criteria; this difference being statistically significant when normalizing at LD, reaching 12% for the 3%/1.5 mm criterion. Conclusion: Both detectors provide satisfactory results for the QA of plans for VMAT lung SBRT. The film provided greater mean GPR values, afforded greater spatial resolution and was more efficient overall. PMID:28974858

Quality assurance of dynamic parameters in volumetric modulated arc therapy

PubMed Central

Manikandan, A; Sarkar, B; Holla, R; Vivek, T R; Sujatha, N

2012-01-01

Objectives The purpose of this study was to demonstrate quality assurance checks for accuracy of gantry speed and position, dose rate and multileaf collimator (MLC) speed and position for a volumetric modulated arc treatment (VMAT) modality (Synergy® S; Elekta, Stockholm, Sweden), and to check that all the necessary variables and parameters were synchronous. Methods Three tests (for gantry position–dose delivery synchronisation, gantry speed–dose delivery synchronisation and MLC leaf speed and positions) were performed. Results The average error in gantry position was 0.5° and the average difference was 3 MU for a linear and a parabolic relationship between gantry position and delivered dose. In the third part of this test (sawtooth variation), the maximum difference was 9.3 MU, with a gantry position difference of 1.2°. In the sweeping field method test, a linear relationship was observed between recorded doses and distance from the central axis, as expected. In the open field method, errors were encountered at the beginning and at the end of the delivery arc, termed the “beginning” and “end” errors. For MLC position verification, the maximum error was −2.46 mm and the mean error was 0.0153 ±0.4668 mm, and 3.4% of leaves analysed showed errors of >±1 mm. Conclusion This experiment demonstrates that the variables and parameters of the Synergy® S are synchronous and that the system is suitable for delivering VMAT using a dynamic MLC. PMID:22745206

Plasma cannabinoid pharmacokinetics following controlled oral delta9-tetrahydrocannabinol and oromucosal cannabis extract administration.

PubMed

Karschner, Erin L; Darwin, W David; Goodwin, Robert S; Wright, Stephen; Huestis, Marilyn A

2011-01-01

Sativex(®), a cannabis extract oromucosal spray containing Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD), is currently in phase III trials as an adjunct to opioids for cancer pain treatment, and recently received United Kingdom approval for treatment of spasticity. There are indications that CBD modulates THC's effects, but it is unclear if this is due to a pharmacokinetic and/or pharmacodynamic interaction. Cannabis smokers provided written informed consent to participate in this randomized, controlled, double-blind, double-dummy institutional review board-approved study. Participants received 5 and 15 mg synthetic oral THC, low-dose (5.4 mg THC and 5.0 mg CBD) and high-dose (16.2 mg THC and 15.0 mg CBD) Sativex, and placebo over 5 sessions. CBD, THC, 11-hydroxy-THC, and 11-nor- 9-carboxy-THC were quantified in plasma by 2-dimensional GC-MS. Lower limits of quantification were ≤0.25 μg/L. Nine cannabis smokers completed all 5 dosing sessions. Significant differences (P < 0.05) in maximum plasma concentrations (C(max)) and areas under the curve from 0-10.5 h postdose (AUC(0→10.5)) for all analytes were found between low and high doses of synthetic THC and Sativex. There were no statistically significant differences in C(max), time to maximum concentration or in the AUC(0→10.5) between similar oral THC and Sativex doses. Relative bioavailability was calculated to determine the relative rate and extent of THC absorption; 5 and 15 mg oral THC bioavailability was 92.6% (13.1%) and 98.8% (11.0%) of low- and high-dose Sativex, respectively. These data suggest that CBD modulation of THC's effects is not due to a pharmacokinetic interaction at these therapeutic doses.

Deferasirox for the treatment of iron overload after allogeneic hematopoietic cell transplantation: multicenter phase I study (KSGCT1302).

PubMed

Tachibana, Takayoshi; Kanda, Junya; Machida, Shinichiro; Saito, Takeshi; Tanaka, Masatsugu; Najima, Yuho; Koyama, Satoshi; Miyazaki, Takuya; Yamamoto, Eri; Takeuchi, Masahiro; Morita, Satoshi; Kanda, Yoshinobu; Kanamori, Heiwa; Okamoto, Shinichiro

2018-05-01

The aim of this study was to assess the safety and optimal dose of deferasirox for the treatment of iron overload after allogeneic hematopoietic cell transplantation (HCT). The primary endpoint was the maximum tolerated dose of deferasirox that was determined by the intrapatient dose escalation methods. A total of 16 patients with post-HCT iron overload were enrolled in the study. After excluding one case of early relapse, 15 remained evaluable. Their median age was 42 years (range 22-68). Median time from HCT to deferasirox administration was 9 months (range 6-84). Deferasirox was started at a dose of 5 mg/kg, and the dose was increased to 7.5 and 10 mg/kg every 4 weeks unless there were no grade ≥ 2 of adverse events. Achievement rates of planned medication were 80% in 5 mg/kg (12 of 15), 73% in 7.5 mg/kg (11 of 15), and 60% in 10 mg/kg (9 of 15), respectively. The reasons for discontinuation of the drug were grade 2 of adverse events (n = 4), late relapse (n = 1), and self-cessation (n = 1). None of the patients developed grade ≥ 3 of adverse events or exacerbation of GVHD. Among 11 evaluable cases, mean value of ferritin decreased from 1560 ng/ml pre-treatment to 1285 ng/ml post-treatment. These data suggested that 10 mg/kg of deferasirox may be maximum tolerated dose when given after HCT. Our dose escalating method of deferasirox is useful to identify the optimal dosage of the drug in each patient. UMIN000011251.

Pharmacokinetics and pharmacodynamics of a human monoclonal anti‐FGF23 antibody (KRN23) in the first multiple ascending‐dose trial treating adults with X‐linked hypophosphatemia

PubMed Central

Imel, Erik A.; Ruppe, Mary D.; Weber, Thomas J.; Klausner, Mark A.; Ito, Takahiro; Vergeire, Maria; Humphrey, Jeffrey; Glorieux, Francis H.; Portale, Anthony A.; Insogna, Karl; Carpenter, Thomas O.; Peacock, Munro

2015-01-01

Abstract In X‐linked hypophosphatemia (XLH), serum fibroblast growth factor 23 (FGF23) is increased and results in reduced renal maximum threshold for phosphate reabsorption (TmP), reduced serum inorganic phosphorus (Pi), and inappropriately low normal serum 1,25 dihydroxyvitamin D (1,25[OH]2D) concentration, with subsequent development of rickets or osteomalacia. KRN23 is a recombinant human IgG1 monoclonal antibody that binds to FGF23 and blocks its activity. Up to 4 doses of KRN23 were administered subcutaneously every 28 days to 28 adults with XLH. Mean ± standard deviation KRN23 doses administered were 0.05, 0.10 ± 0.01, 0.28 ± 0.06, and 0.48 ± 0.16 mg/kg. The mean time to reach maximum serum KRN23 levels was 7.0 to 8.5 days. The mean KRN23 half‐life was 16.4 days. The mean area under the concentration–time curve (AUCn) for each dosing interval increased proportionally with increases in KRN23 dose. The mean intersubject variability in AUCn ranged from 30% to 37%. The area under the effect concentration–time curve (AUECn) for change from baseline in TmP per glomerular filtration rate, serum Pi, 1,25(OH)2D, and bone markers for each dosing interval increased linearly with increases in KRN23 AUCn. Linear correlation between serum KRN23 concentrations and increase in serum Pi support KRN23 dose adjustments based on predose serum Pi concentration. © 2015 The Authors. The Journal of Clinical Pharmacology Published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology PMID:26073451

Plasma Cannabinoid Pharmacokinetics following Controlled Oral Δ9-Tetrahydrocannabinol and Oromucosal Cannabis Extract Administration

PubMed Central

Karschner, Erin L.; Darwin, W. David; Goodwin, Robert S.; Wright, Stephen; Huestis, Marilyn A.

2013-01-01

BACKGROUND Sativex®, a cannabis extract oromucosal spray containing Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), is currently in phase III trials as an adjunct to opioids for cancer pain treatment, and recently received United Kingdom approval for treatment of spasticity. There are indications that CBD modulates THC’s effects, but it is unclear if this is due to a pharmacokinetic and/or pharmacodynamic interaction. METHODS Cannabis smokers provided written informed consent to participate in this randomized, controlled, double-blind, double-dummy institutional review board–approved study. Participants received 5 and 15 mg synthetic oral THC, low-dose (5.4 mg THC and 5.0 mg CBD) and high-dose (16.2 mg THC and 15.0 mg CBD) Sativex, and placebo over 5 sessions. CBD, THC, 11-hydroxy-THC, and 11-nor-9-carboxy-THC were quantified in plasma by 2-dimensional GC-MS. Lower limits of quantification were ≤0.25 μg/L. RESULTS Nine cannabis smokers completed all 5 dosing sessions. Significant differences (P < 0.05) in maximum plasma concentrations (Cmax) and areas under the curve from 0–10.5 h postdose (AUC0→10.5) for all analytes were found between low and high doses of synthetic THC and Sativex. There were no statistically significant differences in Cmax, time to maximum concentration or in the AUC0→10.5 between similar oral THC and Sativex doses. Relative bioavailability was calculated to determine the relative rate and extent of THC absorption; 5 and 15 mg oral THC bioavailability was 92.6% (13.1%) and 98.8% (11.0%) of low- and high-dose Sativex, respectively. CONCLUSION These data suggest that CBD modulation of THC’s effects is not due to a pharmacokinetic interaction at these therapeutic doses. PMID:21078841

ASSESSMENT OF RADON IN SOIL AND WATER IN DIFFERENT REGIONS OF KOLHAPUR DISTRICT, MAHARASHTRA, INDIA.

PubMed

Raste, P M; Sahoo, B K; Gaware, J J; Sharma, Anil; Waikar, M R; Shaikh, A A; Sonkawade, R G

2018-03-19

Researchers have already established that inhalation of high radon concentration is hazardous to human health. Radon concentration has been measured in water and soil, in various part of Kolhapur district has been carried out by the AQTEK Smart RnDuo which is an active device technique. The observed minimum value of the radon mass exhalation rate of the soil is 13.16 ± 0.83 mBq/kg/h and maximum is 35.11 ± 1.84 mBq/kg/h. The minimum value of the Radon concentration in water is 0.33 ± 0.052 Bq/L and maximum is 7.32 ± 0.078 Bq/L. These values of radon concentration are below the action of recommended level by the USEPA, which is set as the maximum contaminant level of 11.1-148 Bq/L of radon in drinking water. Total annual effective dose rate of water is 11 μSv/y. The purpose of present study is to assess radiological risk from consumption of water that provide in Kolhapur district and to evaluate the radon mass exhalation rate of soil in few places of Kolhapur district.

Influence of intravenous opioid dose on postoperative ileus.

PubMed

Barletta, Jeffrey F; Asgeirsson, Theodor; Senagore, Anthony J

2011-07-01

Intravenous opioids represent a major component in the pathophysiology of postoperative ileus (POI). However, the most appropriate measure and threshold to quantify the association between opioid dose (eg, average daily, cumulative, maximum daily) and POI remains unknown. To evaluate the relationship between opioid dose, POI, and length of stay (LOS) and identify the opioid measure that was most strongly associated with POI. Consecutive patients admitted to a community teaching hospital who underwent elective colorectal surgery by any technique with an enhanced-recovery protocol postoperatively were retrospectively identified. Patients were excluded if they received epidural analgesia, developed a major intraabdominal complication or medical complication, or had a prolonged workup prior to surgery. Intravenous opioid doses were quantified and converted to hydromorphone equivalents. Classification and regression tree (CART) analysis was used to determine the dosing threshold for the opioid measure most associated with POI and define high versus low use of opioids. Risk factors for POI and prolonged LOS were determined through multivariate analysis. The incidence of POI in 279 patients was 8.6%. CART analysis identified a maximum daily intravenous hydromorphone dose of 2 mg or more as the opioid measure most associated with POI. Multivariate analysis revealed maximum daily hydromorphone dose of 2 mg or more (p = 0.034), open surgical technique (p = 0.045), and days of intravenous narcotic therapy (p = 0.003) as significant risk factors for POI. Variables associated with increased LOS were POI (p < 0.001), maximum daily hydromorphone dose of 2 mg or more (p < 0.001), and age (p = 0.005); laparoscopy (p < 0.001) was associated with a decreased LOS. Intravenous opioid therapy is significantly associated with POI and prolonged LOS, particularly when the maximum hydromorphone dose per day exceeds 2 mg. Clinicians should consider alternative, nonopioid-based pain management options when this occurs.

Ceritinib in ALK-Rearranged Non–Small-Cell Lung Cancer

PubMed Central

Shaw, Alice T.; Kim, Dong-Wan; Mehra, Ranee; Tan, Daniel S.W.; Felip, Enriqueta; Chow, Laura Q.M.; Camidge, D. Ross; Vansteenkiste, Johan; Sharma, Sunil; De Pas, Tommaso; Riely, Gregory J.; Solomon, Benjamin J.; Wolf, Juergen; Thomas, Michael; Schuler, Martin; Liu, Geoffrey; Santoro, Armando; Lau, Yvonne Y.; Goldwasser, Meredith; Boral, Anthony L.; Engelman, Jeffrey A.

2014-01-01

BACKGROUND Non–small-cell lung cancer (NSCLC) harboring the anaplastic lymphoma kinase gene (ALK) rearrangement is sensitive to the ALK inhibitor crizotinib, but resistance invariably develops. Ceritinib (LDK378) is a new ALK inhibitor that has shown greater antitumor potency than crizotinib in preclinical studies. METHODS In this phase 1 study, we administered oral ceritinib in doses of 50 to 750 mg once daily to patients with advanced cancers harboring genetic alterations in ALK. In an expansion phase of the study, patients received the maximum tolerated dose. Patients were assessed to determine the safety, pharmacokinetic properties, and antitumor activity of ceritinib. Tumor biopsies were performed before ceritinib treatment to identify resistance mutations in ALK in a group of patients with NSCLC who had had disease progression during treatment with crizotinib. RESULTS A total of 59 patients were enrolled in the dose-escalation phase. The maximum tolerated dose of ceritinib was 750 mg once daily; dose-limiting toxic events included diarrhea, vomiting, dehydration, elevated aminotransferase levels, and hypophosphatemia. This phase was followed by an expansion phase, in which an additional 71 patients were treated, for a total of 130 patients overall. Among 114 patients with NSCLC who received at least 400 mg of ceritinib per day, the overall response rate was 58% (95% confidence interval [CI], 48 to 67). Among 80 patients who had received crizotinib previously, the response rate was 56% (95% CI, 45 to 67). Responses were observed in patients with various resistance mutations in ALK and in patients without detectable mutations. Among patients with NSCLC who received at least 400 mg of ceritinib per day, the median progression-free survival was 7.0 months (95% CI, 5.6 to 9.5). CONCLUSIONS Ceritinib was highly active in patients with advanced, ALK-rearranged NSCLC, including those who had had disease progression during crizotinib treatment, regardless of the presence of resistance mutations in ALK. (Funded by Novartis Pharmaceuticals and others; ClinicalTrials.gov number, NCT01283516.) PMID:24670165

Comparison of measured and estimated maximum skin doses during CT fluoroscopy lung biopsies.

PubMed

Zanca, F; Jacobs, A; Crijns, W; De Wever, W

2014-07-01

To measure patient-specific maximum skin dose (MSD) associated with CT fluoroscopy (CTF) lung biopsies and to compare measured MSD with the MSD estimated from phantom measurements, as well as with the CTDIvol of patient examinations. Data from 50 patients with lung lesions who underwent a CT fluoroscopy-guided biopsy were collected. The CT protocol consisted of a low-kilovoltage (80 kV) protocol used in combination with an algorithm for dose reduction to the radiology staff during the interventional procedure, HandCare (HC). MSD was assessed during each intervention using EBT2 gafchromic films positioned on patient skin. Lesion size, position, total fluoroscopy time, and patient-effective diameter were registered for each patient. Dose rates were also estimated at the surface of a normal-size anthropomorphic thorax phantom using a 10 cm pencil ionization chamber placed at every 30°, for a full rotation, with and without HC. Measured MSD was compared with MSD values estimated from the phantom measurements and with the cumulative CTDIvol of the procedure. The median measured MSD was 141 mGy (range 38-410 mGy) while the median cumulative CTDIvol was 72 mGy (range 24-262 mGy). The ratio between the MSD estimated from phantom measurements and the measured MSD was 0.87 (range 0.12-4.1) on average. In 72% of cases the estimated MSD underestimated the measured MSD, while in 28% of the cases it overestimated it. The same trend was observed for the ratio of cumulative CTDIvol and measured MSD. No trend was observed as a function of patient size. On average, estimated MSD from dose rate measurements on phantom as well as from CTDIvol of patient examinations underestimates the measured value of MSD. This can be attributed to deviations of the patient's body habitus from the standard phantom size and to patient positioning in the gantry during the procedure.

NAIRAS aircraft radiation model development, dose climatology, and initial validation.

PubMed

Mertens, Christopher J; Meier, Matthias M; Brown, Steven; Norman, Ryan B; Xu, Xiaojing

2013-10-01

[1] The Nowcast of Atmospheric Ionizing Radiation for Aviation Safety (NAIRAS) is a real-time, global, physics-based model used to assess radiation exposure to commercial aircrews and passengers. The model is a free-running physics-based model in the sense that there are no adjustment factors applied to nudge the model into agreement with measurements. The model predicts dosimetric quantities in the atmosphere from both galactic cosmic rays (GCR) and solar energetic particles, including the response of the geomagnetic field to interplanetary dynamical processes and its subsequent influence on atmospheric dose. The focus of this paper is on atmospheric GCR exposure during geomagnetically quiet conditions, with three main objectives. First, provide detailed descriptions of the NAIRAS GCR transport and dosimetry methodologies. Second, present a climatology of effective dose and ambient dose equivalent rates at typical commercial airline altitudes representative of solar cycle maximum and solar cycle minimum conditions and spanning the full range of geomagnetic cutoff rigidities. Third, conduct an initial validation of the NAIRAS model by comparing predictions of ambient dose equivalent rates with tabulated reference measurement data and recent aircraft radiation measurements taken in 2008 during the minimum between solar cycle 23 and solar cycle 24. By applying the criterion of the International Commission on Radiation Units and Measurements (ICRU) on acceptable levels of aircraft radiation dose uncertainty for ambient dose equivalent greater than or equal to an annual dose of 1 mSv, the NAIRAS model is within 25% of the measured data, which fall within the ICRU acceptable uncertainty limit of 30%. The NAIRAS model predictions of ambient dose equivalent rate are generally within 50% of the measured data for any single-point comparison. The largest differences occur at low latitudes and high cutoffs, where the radiation dose level is low. Nevertheless, analysis suggests that these single-point differences will be within 30% when a new deterministic pion-initiated electromagnetic cascade code is integrated into NAIRAS, an effort which is currently underway.

NAIRAS aircraft radiation model development, dose climatology, and initial validation

NASA Astrophysics Data System (ADS)

Mertens, Christopher J.; Meier, Matthias M.; Brown, Steven; Norman, Ryan B.; Xu, Xiaojing

2013-10-01

The Nowcast of Atmospheric Ionizing Radiation for Aviation Safety (NAIRAS) is a real-time, global, physics-based model used to assess radiation exposure to commercial aircrews and passengers. The model is a free-running physics-based model in the sense that there are no adjustment factors applied to nudge the model into agreement with measurements. The model predicts dosimetric quantities in the atmosphere from both galactic cosmic rays (GCR) and solar energetic particles, including the response of the geomagnetic field to interplanetary dynamical processes and its subsequent influence on atmospheric dose. The focus of this paper is on atmospheric GCR exposure during geomagnetically quiet conditions, with three main objectives. First, provide detailed descriptions of the NAIRAS GCR transport and dosimetry methodologies. Second, present a climatology of effective dose and ambient dose equivalent rates at typical commercial airline altitudes representative of solar cycle maximum and solar cycle minimum conditions and spanning the full range of geomagnetic cutoff rigidities. Third, conduct an initial validation of the NAIRAS model by comparing predictions of ambient dose equivalent rates with tabulated reference measurement data and recent aircraft radiation measurements taken in 2008 during the minimum between solar cycle 23 and solar cycle 24. By applying the criterion of the International Commission on Radiation Units and Measurements (ICRU) on acceptable levels of aircraft radiation dose uncertainty for ambient dose equivalent greater than or equal to an annual dose of 1 mSv, the NAIRAS model is within 25% of the measured data, which fall within the ICRU acceptable uncertainty limit of 30%. The NAIRAS model predictions of ambient dose equivalent rate are generally within 50% of the measured data for any single-point comparison. The largest differences occur at low latitudes and high cutoffs, where the radiation dose level is low. Nevertheless, analysis suggests that these single-point differences will be within 30% when a new deterministic pion-initiated electromagnetic cascade code is integrated into NAIRAS, an effort which is currently underway.

NAIRAS aircraft radiation model development, dose climatology, and initial validation

PubMed Central

Mertens, Christopher J; Meier, Matthias M; Brown, Steven; Norman, Ryan B; Xu, Xiaojing

2013-01-01

[1] The Nowcast of Atmospheric Ionizing Radiation for Aviation Safety (NAIRAS) is a real-time, global, physics-based model used to assess radiation exposure to commercial aircrews and passengers. The model is a free-running physics-based model in the sense that there are no adjustment factors applied to nudge the model into agreement with measurements. The model predicts dosimetric quantities in the atmosphere from both galactic cosmic rays (GCR) and solar energetic particles, including the response of the geomagnetic field to interplanetary dynamical processes and its subsequent influence on atmospheric dose. The focus of this paper is on atmospheric GCR exposure during geomagnetically quiet conditions, with three main objectives. First, provide detailed descriptions of the NAIRAS GCR transport and dosimetry methodologies. Second, present a climatology of effective dose and ambient dose equivalent rates at typical commercial airline altitudes representative of solar cycle maximum and solar cycle minimum conditions and spanning the full range of geomagnetic cutoff rigidities. Third, conduct an initial validation of the NAIRAS model by comparing predictions of ambient dose equivalent rates with tabulated reference measurement data and recent aircraft radiation measurements taken in 2008 during the minimum between solar cycle 23 and solar cycle 24. By applying the criterion of the International Commission on Radiation Units and Measurements (ICRU) on acceptable levels of aircraft radiation dose uncertainty for ambient dose equivalent greater than or equal to an annual dose of 1 mSv, the NAIRAS model is within 25% of the measured data, which fall within the ICRU acceptable uncertainty limit of 30%. The NAIRAS model predictions of ambient dose equivalent rate are generally within 50% of the measured data for any single-point comparison. The largest differences occur at low latitudes and high cutoffs, where the radiation dose level is low. Nevertheless, analysis suggests that these single-point differences will be within 30% when a new deterministic pion-initiated electromagnetic cascade code is integrated into NAIRAS, an effort which is currently underway. PMID:26213513

MEASUREMENT OF RADIATION DOSES TO THE EYE LENS DURING ORTHOPEDIC SURGERY USING AN C-ARM X-RAY SYSTEM.

PubMed

Suzuki, Akira; Matsubara, Kosuke; Sasa, Yuko

2018-04-01

The present study aimed to determine doses delivered to the eye lenses of surgeons while using the inverted-C-arm technique and the protective effect of leaded spectacles during orthopedic surgery. The kerma in air was measured at five positions on leaded glasses positioned near the eye lens and on the neck using small optically stimulated luminescence (OSL) dosemeters. The lens equivalent dose was also measured at the neck using an OSL dosemeter. The maximum equivalent dose to the eye lens and the maximum kerma were 0.8 mSv/month and 0.66 mGy/month, respectively. The leaded glasses reduced the exposure by ~60%. Even if the surgeons are exposed to the maximum dose of X-ray radiation for 5 years, the equivalent doses to the eye lens will not exceed the present limit recommended by the ICRP.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marsh, I; Otto, M; Weichert, J

Purpose: The focus of this work is to perform Monte Carlo-based dosimetry for several pediatric cancer xenografts in mice treated with a novel radiopharmaceutical {sup 131}I-CLR1404. Methods: Four mice for each tumor cell line were injected with 8–13 µCi/g of the {sup 124}124I-CLR1404. PET/CT images of each individual mouse were acquired at 5–6 time points over the span of 96–170 hours post-injection. Following acquisition, the images were co-registered, resampled, rescaled, corrected for partial volume effects (PVE), and masked. For this work the pre-treatment PET images of {sup 124}I-CLR1404 were used to predict therapeutic doses from {sup 131}I-CLR1404 at each timemore » point by assuming the same injection activity and accounting for the difference in physical decay rates. Tumors and normal tissues were manually contoured using anatomical and functional images. The CT and the PET images were used in the Geant4 (v9.6) Monte Carlo simulation to define the geometry and source distribution, respectively. The total cumulated absorbed dose was calculated by numerically integrating the dose-rate at each time point over all time on a voxel-by-voxel basis. Results: Spatial distributions of the absorbed dose rates and dose volume histograms as well as mean, minimum, maximum, and total dose values for each ROI were generated for each time point. Conclusion: This work demonstrates how mouse-specific MC-based dosimetry could potentially provide more accurate characterization of efficacy of novel radiopharmaceuticals in radionuclide therapy. This work is partially funded by NIH grant CA198392.« less

[Study of the consequences to the health of the Urkutsk Region's population from nuclear explosions at the Semipalatinsk testing site].

PubMed

Rukavishnikov, V S; Efimova, N V; Katul'skaia, O Iu; Cherniago, B P; Matorova, N I; Beliaeva, T A; Medvedev, V I

2009-01-01

Analysis of archival records on the activity of diurnal plane-tables from the region's weather stations revealed local radioactive fall-out in the near-Baikal areas from the nuclear weapon tests carried out at the Semipalatinsk testing site. Examination of mortality rates in the settlements exposed to the tests showed that the maximum rates of overall and lung malignancy mortalities were observed in 1960-1979; the mean radiation dose in the exposed settlements were estimated to be 580-850 MeV.

Direct measurement of a patient's entrance skin dose during pediatric cardiac catheterization

PubMed Central

Sun, Lue; Mizuno, Yusuke; Iwamoto, Mari; Goto, Takahisa; Koguchi, Yasuhiro; Miyamoto, Yuka; Tsuboi, Koji; Chida, Koichi; Moritake, Takashi

2014-01-01

Children with complex congenital heart diseases often require repeated cardiac catheterization; however, children are more radiosensitive than adults. Therefore, radiation-induced carcinogenesis is an important consideration for children who undergo those procedures. We measured entrance skin doses (ESDs) using radio-photoluminescence dosimeter (RPLD) chips during cardiac catheterization for 15 pediatric patients (median age, 1.92 years; males, n = 9; females, n = 6) with cardiac diseases. Four RPLD chips were placed on the patient's posterior and right side of the chest. Correlations between maximum ESD and dose–area products (DAP), total number of frames, total fluoroscopic time, number of cine runs, cumulative dose at the interventional reference point (IRP), body weight, chest thickness, and height were analyzed. The maximum ESD was 80 ± 59 (mean ± standard deviation) mGy. Maximum ESD closely correlated with both DAP (r = 0.78) and cumulative dose at the IRP (r = 0.82). Maximum ESD for coiling and ballooning tended to be higher than that for ablation, balloon atrial septostomy, and diagnostic procedures. In conclusion, we directly measured ESD using RPLD chips and found that maximum ESD could be estimated in real-time using angiographic parameters, such as DAP and cumulative dose at the IRP. Children requiring repeated catheterizations would be exposed to high radiation levels throughout their lives, although treatment influences radiation dose. Therefore, the radiation dose associated with individual cardiac catheterizations should be analyzed, and the effects of radiation throughout the lives of such patients should be followed. PMID:24968708

Bone fractures following external beam radiotherapy and limb-preservation surgery for lower extremity soft tissue sarcoma: relationship to irradiated bone length, volume, tumor location and dose.

PubMed

Dickie, Colleen I; Parent, Amy L; Griffin, Anthony M; Fung, Sharon; Chung, Peter W M; Catton, Charles N; Ferguson, Peter C; Wunder, Jay S; Bell, Robert S; Sharpe, Michael B; O'Sullivan, Brian

2009-11-15

To examine the relationship between tumor location, bone dose, and irradiated bone length on the development of radiation-induced fractures for lower extremity soft tissue sarcoma (LE-STS) patients treated with limb-sparing surgery and radiotherapy (RT). Of 691 LE-STS patients treated from 1989 to 2005, 31 patients developed radiation-induced fractures. Analysis was limited to 21 fracture patients (24 fractures) who were matched based on tumor size and location, age, beam arrangement, and mean total cumulative RT dose to a random sample of 53 nonfracture patients and compared for fracture risk factors. Mean dose to bone, RT field size (FS), maximum dose to a 2-cc volume of bone, and volume of bone irradiated to >or=40 Gy (V40) were compared. Fracture site dose was determined by comparing radiographic images and surgical reports to fracture location on the dose distribution. For fracture patients, mean dose to bone was 45 +/- 8 Gy (mean dose at fracture site 59 +/- 7 Gy), mean FS was 37 +/- 8 cm, maximum dose was 64 +/- 7 Gy, and V40 was 76 +/- 17%, compared with 37 +/- 11 Gy, 32 +/- 9 cm, 59 +/- 8 Gy, and 64 +/- 22% for nonfracture patients. Differences in mean, maximum dose, and V40 were statistically significant (p = 0.01, p = 0.02, p = 0.01). Leg fractures were more common above the knee joint. The risk of radiation-induced fracture appears to be reduced if V40 <64%. Fracture incidence was lower when the mean dose to bone was <37 Gy or maximum dose anywhere along the length of bone was <59 Gy. There was a trend toward lower mean FS for nonfracture patients.

Heart Rate Variability (HRV) modifications in adult hemiplegic patients after botulinum toxin type A (nt-201) injection.

PubMed

Invernizzi, M; Carda, S; Molinari, C; Stagno, D; Cisari, C; Baricich, A

2015-08-01

The most important adverse effect of BoNT-A is the systemic diffusion of the toxin. There is some evidence that the administration of high doses can increase the risk of systemic diffusion and the development of clinically evident adverse effects, however an international consensus does not exist about its maximum dose. The aim of this study was to evaluate changes in autonomic heart drive induced by high doses (higher than 600 units) of incobotulinumtoxinA injection in spastic stroke patients. Moreover, the treatment safety by monitoring adverse events occurrence was assessed. Case control study. Eleven stroke survivors with spastic hemiplegia. Patients were treated with intramuscular focal injections of IncobotulinumtoxinA (NT 201; Xeomin®, Merz Pharmaceuticals GmbH, Frankfurt, Germany). Doses were below 12 units/Kg. Each patient underwent an ECG recording before injection and 10 days after treatment. Linear and non-linear Heart Rate variability (HRV) measures were derived from ECGs with a dedicated software. None of the variable considered showed statistically significant changes after BoNT-A injection. The use of incobotulinumtoxinA in adult patients at doses up to 12 units/kg seems to be safe regarding autonomic heart drive. The use of IncobotulinumtoxinA up to 600 units could be a safe therapeutic option in spastic hemiplegic stroke survivors.

DOSE-RATE DEPENDENCE OF INSTANTANEOUS PHYSIOLOGICAL RADIATION EFFECTS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hug, O.

Nastic movements in Mimosa pudica were induced by x radiation. Using short radiation impulses of 10 to 30 sec and doses up to 120 kr/min, the leaflets were observed to close and the stem to bend in the main joint during the first minute. After irradiation of parts of the leaflet, the reaction spreads along the physiological pathways as in any other stimulus. When the action potential is completed, slow depolarization continues and reaches a maximum, finally returning to the initial value in about two hr. The effect was found to be dose- dependent. It is hypothesized that either amore » direct physicochemical change of the cell membrane or a damage of substances which influence the function of the cell membrane is induced by the irradiation. (H.M.G.)« less

Preliminary analysis of the implications of natural radiations on geostationary operations

NASA Technical Reports Server (NTRS)

Wilson, J. W.; Denn, F. M.

1976-01-01

The natural radiations present at geostationary orbit are discussed. Low-level galactic cosmic rays are important for careers spending a year or more at geostationary altitude. Trapped radiation will on occasion require interruption of extravehicular activity (EVA). The spacesuit shield requirements are strongly affected by the number of interruptions allowed. EVA cannot proceed during a large solar event and maximum allowable doses are exceeded in a few hours unless a heavily shielded area is provided. A shelter of 10 g/sq cm with personal shielding for the eyes and testes would contain exposure to within the presently accepted exposure constraints. Since radiation levels can increase unexpectedly to serious levels, an onboard radiation monitoring system with rate and integration capabilities is required for both surface-dose and depth-dose monitoring.

A dose escalation feasibility study of lenalidomide for treatment of symptomatic, relapsed chronic lymphocytic leukemia☆

PubMed Central

Maddocks, Kami; Ruppert, Amy S.; Browning, Rebekah; Jones, Jeffrey; Flynn, Joseph; Kefauver, Cheryl; Gao, Yue; Jiang, Yao; Rozewski, Darlene M.; Poi, Ming; Phelps, Mitch A.; Harper, Erica; Johnson, Amy J.; Byrd, John C.; Andritsos, Leslie A.

2015-01-01

Adequate dosing of lenalidomide in Chronic Lymphocytic Leukemia (CLL) remains unclear. This study determined maximum tolerated dose (MTD) in relapsed CLL patients (Cohort A) and patients achieving a partial response (PR) or better to recent therapy (Cohort B). Thirty-seven patients were enrolled. MTD was 2.5 mg followed by 5.0 mg continuous. In Cohort A, tumor flare grade 1–2 occurred in 15 patients (50%) and grade 3 in 1 patient (3%). Cohort A had 19 of 23 evaluable (83%) patients, 4 PR (17%) and 15 (65%) stable disease (SD), Cohort B had 6 of 7 patients (86%) with SD. Despite overall response rate not being high, many patients remained on therapy several months with SD. PMID:25082342

Incidence of colorectal cancer in new users and non-users of low-dose aspirin without existing cardiovascular disease: A cohort study using The Health Improvement Network.

PubMed

Cea Soriano, Lucía; Soriano-Gabarró, Montse; García Rodríguez, Luis A

2017-12-01

Evidence regarding the chemo-protective effects of aspirin has influenced expert opinion in favour of low-dose aspirin use in certain patient populations without cardiovascular disease (CVD). The effects of aspirin in reducing the incidence of colorectal cancer (CRC) may be a large contributor to this favourable risk-benefit profile of low-dose aspirin in primary CVD prevention. Using The Health Improvement Network, we estimated the incidence of CRC in individuals free of CVD and either prescribed or not prescribed prophylactic low-dose aspirin. Two cohorts - new-users of low-dose aspirin (N=109,426) and a comparator cohort of non-users (N=154,056) at start of follow-up - were followed (maximum 13years) to identify incident CRC cases. Individuals with a record of CVD, cancer or low-dose aspirin prescription before start of follow-up were excluded. 2330 incident cases of CRC occurred; 885 in the aspirin cohort and 1445 in the comparator cohort, after mean follow-ups of 5.43years and 5.17years, respectively. Incidence rates of CRC per 10,000 person-years (95% confidence interval) were 14.90 (13.95-15.92) in the aspirin cohort and 18.15 (17.24-19.12) in the comparator cohort; incidence rate ratio 0.82 (0.76-0.89) adjusted for age, sex and primary care practitioner (PCP) visits in the previous year. Lower incidence rates were seen in the aspirin cohort for all strata evaluated (gender, age group and number of PCP visits in the previous year) except those aged ≥80years. Among most individuals without established CVD, initiation of low-dose aspirin is associated with a reduced incidence of CRC. Copyright © 2017 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Whitaker, Thomas J., E-mail: whitaker.thomas@mayo.edu; Beltran, Chris; Tryggestad, Erik

Purpose: Delayed charge is a small amount of charge that is delivered to the patient after the planned irradiation is halted, which may degrade the quality of the treatment by delivering unwarranted dose to the patient. This study compares two methods for minimizing the effect of delayed charge on the dose delivered with a synchrotron based discrete spot scanning proton beam. Methods: The delivery of several treatment plans was simulated by applying a normally distributed value of delayed charge, with a mean of 0.001(SD 0.00025) MU, to each spot. Two correction methods were used to account for the delayed charge.more » Method one (CM1), which is in active clinical use, accounts for the delayed charge by adjusting the MU of the current spot based on the cumulative MU. Method two (CM2) in addition reduces the planned MU by a predicted value. Every fraction of a treatment was simulated using each method and then recomputed in the treatment planning system. The dose difference between the original plan and the sum of the simulated fractions was evaluated. Both methods were tested in a water phantom with a single beam and simple target geometry. Two separate phantom tests were performed. In one test the dose per fraction was varied from 0.5 to 2 Gy using 25 fractions per plan. In the other test the number fractions were varied from 1 to 25, using 2 Gy per fraction. Three patient plans were used to determine the effect of delayed charge on the delivered dose under realistic clinical conditions. The order of spot delivery using CM1 was investigated by randomly selecting the starting spot for each layer, and by alternating per layer the starting spot from first to last. Only discrete spot scanning was considered in this study. Results: Using the phantom setup and varying the dose per fraction, the maximum dose difference for each plan of 25 fractions was 0.37–0.39 Gy and 0.03–0.05 Gy for CM1 and CM2, respectively. While varying the total number of fractions, the maximum dose difference increased at a rate of 0.015 Gy and 0.0018 Gy per fraction for CM1 and CM2, respectively. For CM1, the largest dose difference was found at the location of the first spot in each energy layer, whereas for CM2 the difference in dose was small and showed no dependence on location. For CM1, all of the fields in the patient plans had an area where their excess dose overlapped. No such correlation was found when using CM2. Randomly selecting the starting spot reduces the maximum dose difference from 0.708 to 0.15 Gy. Alternating between first and last spot reduces the maximum dose difference from 0.708 to 0.37 Gy. In the patient plans the excess dose scaled linearly at 0.014 Gy per field per fraction for CM1 and standard delivery order. Conclusions: The predictive model CM2 is superior to a cumulative irradiation model CM1 for minimizing the effects of delayed charge, particularly when considering maximal dose discrepancies and the potential for unplanned hot-spots. This study shows that the dose discrepancy potentially scales at 0.014 Gy per field per fraction for CM1.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bronskill, M.J.

The spatial distribution of radioactivity in the injection site, and its rate of clearance, have been measured in patients undergoing various types of interstitial radiocolloid lymphoscintigraphy using 99mTc-antimony sulfide colloid. The clearance of radioactivity from the injection site, and the expansion with time of the localized radioactivity vary considerably for different sites of injection. Maximum absorbed dose estimates of 45.6 rads to the center of the injection site (rectus sheath) and 21 rads to individual lymph nodes have been calculated for patients undergoing internal mammary lymphoscintigraphy with 450 mu Ci injected radioactivity. Absorbed dose estimates for finger web, toe web,more » and perianal injection sites are also presented.« less

SU-F-T-430: Validation of IBEAM Evo Couch Top for Different Relative Electron Density (RED) Combination During Photon Beam Dose Calculation in Monaco− Treatment Planning System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Manigandan, D; Kumar, M; Mohandas, P

Purpose: Validation of iBEAM™ evo couch-top for different relative electron density (RED) combination during photon beam dose calculation in Monaco− TPS. Methods: The iBEAM™ evo couch-top has two layers:outer carbon fiber (CF) and inner foam core (FC). To study the beam intensity attenuation of couch-top, measured doses were compared with doses calculated for different REDs. Measurements were performed in solid water phantom with PTW-0.125cc ion-chamber positioned at center of the phantom with 5.3cm thickness slabs placed above and below the chamber. Similarly, in TPS, iBEAM™ evo couch-top was simulated and doses were calculated for different RED combinations (0.2CF-0.2FC, 0.4CF-0.2FC, 0.6CF-0.2FC,more » 0.8CF-0.2FC, and 1.0CF-0.2FC) by using Monte Carlo dose calculation algorithm in Monaco TPS (V5.1). Doses were measured for every 10 degree gantry angle separation, 10×10cm{sup 2} field size and 6MV photons. Then, attenuation is defined as the ratio of output at posterior gantry angle to output of its opposed anterior gantry angle (e.g.225°/45°). output fluctuation with different gantry angle was within ±0.21%. To confirm above results, dose-planes were measured for five pelvic VMAT plans (360°arc) in PTW two-dimensional array and compared with different calculated dose-planes of above-mentioned couch REDs. Gamma pass rates<1.00) were analyzed for 3%/2mm criteria. Results: Measured and calculated attenuation was in good agreement for the RED combination of 0.2CF-0.2FC and difference was within ±0.515%. However, other density combination showed difference of ±0.9841%, ±1.667%, ±2.9241% and ±2.8832% for 0.4CF-0.2FC, 0.6CF-0.2FC, 0.8CF-0.2FC, and 1.0CF-0.2FC, respectively. Maximum couch-top attenuation was observed at 110°–120° and 240°–250° and decreases linearly as the gantry angle approaches 180°. Moreover, gamma pass rate confirmed the above results and showed maximum pass rate of 96.23% for 0.2CF-0.2FC, whereas others were 95.72%, 95.12%, 94.31% and 93.24%. Conclusion: RED value of 0.2CF-0.2FC was found to be suitable for accurate couch-top modeling for 6MV photon beam Monte Carlo calculations in Monaco TPS.« less

The pharmacokinetics of pyridostigmine and 3-hydroxy-N-methylpyridinium in the rat: dose-dependent effects after portal vein administration.

PubMed Central

Barber, H E; Bourne, G R; Calvey, T N; Muir, K T

1975-01-01

1 The elimination kinectis of [14C]-pyridostigmine iodine and [14-C-methyl]-3-hydroxypyridinium bromide (3-OH NMP) have been studied in the rat. 2 For pyridostigmine, at a given dose level, the fraction of the dose eliminated unchanged was reduced and the metabolite fraction was increased after portal vein administration when compared to jugular vein administration. This indicates that pyridostigmine is subject to metabolism during the first passage through the liver. 3 When doses of pyridostigmine 1.25 mumol/kg and higher were injected via the portal vein, the proportion excreted in urine as unchanged drug remained constant; in contrast, the percentage of the dose eliminated as the metabolite was significantly reduced. This indicates that a dose-dependent process is involved in the urinary excretion of 3-OH NMP. 4 This conclusion was supported by studies involving the portal and systemic venous injection of 3-OH NMP at different dose levels. After 4 h, approximately85% of the lowest dose was eliminated unchanged in ug this period. The proportion of the dose eliminated in urine was not related to the route of administration. 5 After the injection of pyridostigmine into the jugular vein, the initial rate of drug excretion fell rapidly for approximately 10 min; in contrast, after injection into the portal vein, the rate of excretion of the drug rose to a maximum at 30 minutes. This suggests that the hepatoportal system behaves as a distinct region during the distribution of this drug. PMID:173444

Cosmic Radiation Exposure of Future Hypersonic Flight Missions.

PubMed

Koops, L

2017-06-15

Cosmic radiation exposure in air traffic grows with flight altitude, geographical latitude and flight time. For future high-speed intercontinental point-to-point travel, the trade-off between reduced flight time and enhanced dose rate at higher flight altitudes is investigated. Various representative (partly) hypersonic cruise missions are considered and in dependence on solar activity the integral route dose is calculated for envisaged flight profiles and trajectories. Our results are compared to those for corresponding air connections served by present day subsonic airliners. During solar maximum, we find a significant reduction in route dose for all considered high-speed missions compared to the subsonic reference. However, during solar minimum, comparable or somewhat larger doses result on transpolar trajectories with (partly) hypersonic cruise at Mach 5. Both solar activity and routing are hence found to determine, whether passengers can profit from shorter flight times in terms of radiation exposure, despite of altitude-induced higher dose rates. Yet, aircrews with fixed number of block hours are always subject to larger annual doses, which in the considered cases take values up to five times the reference. We comment on the implications of our results for route planning and aviation decision-making in the absence of radiation shielding solutions. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The small-animal radiation research platform (SARRP): dosimetry of a focused lens system.

PubMed

Deng, Hua; Kennedy, Christopher W; Armour, Elwood; Tryggestad, Erik; Ford, Eric; McNutt, Todd; Jiang, Licai; Wong, John

2007-05-21

A small animal radiation platform equipped with on-board cone-beam CT and conformal irradiation capabilities is being constructed for translational research. To achieve highly localized dose delivery, an x-ray lens is used to focus the broad beam from a 225 kVp x-ray tube down to a beam with a full width half maximum (FWHM) of approximately 1.5 mm in the energy range 40-80 keV. Here, we report on the dosimetric characteristics of the focused beam from the x-ray lens subsystem for high-resolution dose delivery. Using the metric of the average dose within a 1.5 mm diameter area, the dose rates at a source-to-surface distance (SSD) of 34 cm are 259 and 172 cGy min(-1) at 6 mm and 2 cm depths, respectively, with an estimated uncertainty of +/-5%. The per cent depth dose is approximately 56% at 2 cm depth for a beam at 34 cm SSD.

Modeling adverse event counts in phase I clinical trials of a cytotoxic agent.

PubMed

Muenz, Daniel G; Braun, Thomas M; Taylor, Jeremy Mg

2018-05-01

Background/Aims The goal of phase I clinical trials for cytotoxic agents is to find the maximum dose with an acceptable risk of severe toxicity. The most common designs for these dose-finding trials use a binary outcome indicating whether a patient had a dose-limiting toxicity. However, a patient may experience multiple toxicities, with each toxicity assigned an ordinal severity score. The binary response is then obtained by dichotomizing a patient's richer set of data. We contribute to the growing literature on new models to exploit this richer toxicity data, with the goal of improving the efficiency in estimating the maximum tolerated dose. Methods We develop three new, related models that make use of the total number of dose-limiting and low-level toxicities a patient experiences. We use these models to estimate the probability of having at least one dose-limiting toxicity as a function of dose. In a simulation study, we evaluate how often our models select the true maximum tolerated dose, and we compare our models with the continual reassessment method, which uses binary data. Results Across a variety of simulation settings, we find that our models compare well against the continual reassessment method in terms of selecting the true optimal dose. In particular, one of our models which uses dose-limiting and low-level toxicity counts beats or ties the other models, including the continual reassessment method, in all scenarios except the one in which the true optimal dose is the highest dose available. We also find that our models, when not selecting the true optimal dose, tend to err by picking lower, safer doses, while the continual reassessment method errs more toward toxic doses. Conclusion Using dose-limiting and low-level toxicity counts, which are easily obtained from data already routinely collected, is a promising way to improve the efficiency in finding the true maximum tolerated dose in phase I trials.

Comparative Study of Oral and Vaginal Misoprostol for Induction of Labour, Maternal and Foetal Outcome

PubMed Central

Komala, Kambhampati; Reddy, Meherlatha; Quadri, Iqbal Jehan; B., Suneetha; V., Ramya

2013-01-01

Background: Misoprostol is a new promising agent for cervical ripening and induction of labour .The ideal dose, route and frequency of administration of misoprostol are still under investigation. Although, vaginal application of misoprostol has been validated as a reasonable mean of induction, there is a patient resistance to digital examination and there is a risk of ascending infection. For this reason, oral administration of misoprostol for cervical ripening and labour induction has been tried. Aims and Objectives: To compare 50μg of oral misoprostol versus 25μg of intravaginal misoprostol for induction of labour at term and maternal, foetal outcomes. Methods: Two hundred women who were at term, with indication for induction of labour and Bishop scores of ≤5 were randomly assigned to receive misoprostol 50μg or 25μg intravaginal, every 4-6 hours, for a maximum of 5 doses. In either group, pregnant females with inadequate uterine contractions despite being given maximum 5 doses of misoprostol, were augmented using oxytocin. The primary outcome measure was time-interval from induction to vaginal delivery and vaginal delivery rate within 24 hours. Results: The median induction to vaginal delivery time in oral group (12.92h) and vaginal group (14.04 h) was not significant. Oral misoprostol resulted in more number of vaginal deliveries as compared to vaginal misoprostol (94% as compared to 86%), which was not significant. There was a significantly higher incidence of uterine tachysystole in the vaginal group, as compared to oral group. There were no significant differences between the groups with respect to oxytocin augmentation, caesarean section rate, analgesic requirement and neonatal outcome. Conclusion: Oral misoprostol is as efficacious as vaginal misoprostol because of shorter induction delivery interval, lower caesarean section rates, and lower incidence of failed induction rates. Lower incidence of foetal distress and easy intake are observed if the drug is administered orally. PMID:24551660

Dissipation kinetics and safety evaluation of tebuconazole and trifloxystrobin in tea under tropical field conditions.

PubMed

Paramasivam, Mariappan; Deepa, Manthirachalam; Selvi, Chellamuthu; Chandrasekaran, Subramanian

2017-12-01

Dissipation kinetics of tebuconazole, trifloxystrobin and its acid metabolite residues were studied in tea under tropical field conditions using GC-MS (SIM). The average recoveries ranged from 80.7% to 105.8%, with a RSD of <9.3%. Dissipation rate for both doses applied followed first-order kinetics, with half-lives in green leaves in the range of 2.8-3.3 and 2.9-3.3 days; ranges in processed tea were 2.7-3.6 days for trifloxystrobin and 3.0-3.1 days for tebuconazole. The trifloxystrobin residues were not transferred into the tea infusion during the infusion process; tebuconazole did transfer, in the range of 14.3-18.9%. As the theoretical maximum residue contributions on tea from initial deposits were found to be less than the maximum permissible intake values, at the recommended application dose a withdrawal period of 23 days before consumption should be applied to reduce risk.

Lacosamide cardiac safety: a thorough QT/QTc trial in healthy volunteers.

PubMed

Kropeit, D; Johnson, M; Cawello, W; Rudd, G D; Horstmann, R

2015-11-01

To determine whether lacosamide prolongs the corrected QT interval (QTc). In this randomized, double-blind, positive- and placebo-controlled, parallel-design trial, healthy volunteers were randomized to lacosamide 400 mg/day (maximum-recommended daily dose, 6 days), lacosamide 800 mg/day (supratherapeutic dose, 6 days), placebo (6 days), or moxifloxacin 400 mg/day (3 days). Variables included maximum time-matched change from baseline in QT interval individually corrected for heart rate ([HR] QTcI), other ECG parameters, pharmacokinetics (PK), and safety/tolerability. The QTcI mean maximum difference from placebo was -4.3 ms and -6.3 ms for lacosamide 400 and 800 mg/day; upper limits of the 2-sided 90% confidence interval were below the 10 ms non-inferiority margin (-0.5 and -2.5 ms, respectively). Placebo-corrected QTcI for moxifloxacin was +10.4 ms (lower 90% confidence bound >0 [6.6 ms]), which established assay sensitivity for this trial. As lacosamide did not increase QTcI, the trial is considered a negative QTc trial. There was no dose-related or clinically relevant effect on QRS duration. HR increased from baseline by ~5 bpm with lacosamide 800 mg/day versus placebo. Placebo-subtracted mean increases in PR interval at tmax were 7.3 ms (400 mg/day) and 11.9 ms (800 mg/day). There were no findings of second-degree or higher atrioventricular block. Adverse events (AEs) were dose related and most commonly involved the nervous and gastrointestinal systems. Lacosamide (≤ 800 mg/day) did not prolong the QTc interval. Lacosamide caused a small, dose-related increase in mean PR interval that was not associated with AEs. Cardiac, overall safety, and PK profiles for lacosamide in healthy volunteers were consistent with those observed in patients with partial-onset seizures. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Intracoronary Adenosine: Dose-Response Relationship With Hyperemia.

PubMed

Adjedj, Julien; Toth, Gabor G; Johnson, Nils P; Pellicano, Mariano; Ferrara, Angela; Floré, Vincent; Di Gioia, Giuseppe; Barbato, Emanuele; Muller, Olivier; De Bruyne, Bernard

2015-09-01

The present study sought to establish the dosage of intracoronary (IC) adenosine associated with minimal side effects and above which no further increase in flow can be expected. Despite the widespread adoption of IC adenosine in clinical practice, no wide-ranging, dose-response study has been conducted. A recurring debate still exists regarding its optimal dose. In 30 patients, Doppler-derived flow velocity measurements were obtained in 10 right coronary arteries (RCAs) and 20 left coronary arteries (LCAs) free of stenoses >20% in diameter. Flow velocity was measured at baseline and after 8 ml bolus administrations of arterial blood, saline, contrast medium, and 9 escalating doses of adenosine (4 to 500 μg). The hyperemic value was expressed in percent of the maximum flow velocity reached in a given artery (Q/Qmax, %). Q/Qmax did not increase significantly beyond dosages of 60 μg for the RCA and 160 μg for LCA. Heart rate did not change, whereas mean arterial blood pressure decreased by a maximum of 7% (p < 0.05) after bolus injections of IC adenosine. The incidence of transient A-V blocks was 40% after injection of 100 μg in the RCA and was 15% after injection of 200 μg in the LCA. The duration of the plateau reached 12 ± 13 s after injection of 100 μg in the RCA and 21 ± 6 s after the injection of 200 μg in the LCA. A progressive prolongation of the time needed to return to baseline was observed. Hyperemic response after injection of 8 ml of contrast medium reached 65 ± 36% of that achieved after injection of 200 μg of adenosine. This wide-ranging, dose-response study indicates that an IC adenosine bolus injection of 100 μg in the RCA and 200 μg in the LCA induces maximum hyperemia while being associated with minimal side effects. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

MPC and ALI: their basis and their comparison

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kennedy, W.E. Jr.; Watson, E.C.

Radiation protection regulations in the United States have evolved from the recommendations of the International Commission on Radiological Protection (ICRP) and the National Council on Radiation Protection and Measurements (NCRP). In 1959, the ICRP issued Publication 2 which contained specific recommendations on dose rate limits, permissible body burdens, metabolic data for radionuclides, and maximum permissible concentrations (MPC) in air or water. Over the next 20 years, new information became available concerning the effects of radiation, the uptake and retention of radionuclides, and the radioactive decay schemes of parent radionuclides. To include this newer information, the ICRP issued Publication 30 inmore » 1978 to supersede Publication 2. One of the secondary limits defined in Publication 30 is the annual limit of intake (ALI). Radionuclide specific ALI values are intended to replace MPC values in determining whether or not ambient air and water concentrations are sufficiently low to maintain the dose to workers within accepted dose rate limits. In this paper, we discuss the derivation of MPC and ALI values, compare inhalation committed dose equivalent factors derived from ICRP Publications 2 and 30, and discuss the practical implications of using either MPC or ALI in determining compliance with occupational exposure limits. 6 references.« less

Modeling marrow damage from response data: Evolution from radiation biology to benzene toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jones, T.D.; Morris, M.D.; Hasan, J.S.

1996-12-01

Consensus principles from radiation biology were used to describe a generic set of nonlinear, first-order differential equations for modeling toxicity-induced compensatory cell kinetics in terms of sublethal injury, repair, direct killing, killing of cells with unrepaired sublethal injury, and repopulation. This cellular model was linked to a probit model of hematopoietic mortality that describes death from infection and/or hemorrhage between 5 and 30 days. Mortality data from 27 experiments with 851 dose-response groups, in which doses were protracted by rate and/or fractionation, were used to simultaneously estimate all rate constants by maximum-likelihood methods. Data used represented 18,940 test animals: 12,827more » mice, 2925 rats, 1676 sheep, 829 swine, 479 dogs, and 204 burros. Although a long-term, repopulating hematopoietic stem cell is ancestral to all lineages needed to restore normal homeostasis, the dose-response data from the protracted irradiations indicate clearly that the particular lineage that is critical to hematopoietic recovery does not resemble stemlike cells with regard to radiosensitivity and repopulation rates. Instead, the weakest link in the chain of hematopoiesis was found to have an intrinsic radioresistance equal to or greater than stromal cells and to repopulate at the same rates. Model validation has been achieved by predicting the LD50 and/or fractional group mortality in 38 protracted-dose experiments (rats and mice) that were not used in the fitting of model coefficients. 29 refs., 5 figs., 5 tabs.« less

Carbon-ion re-irradiation for recurrences after initial treatment of stage I non-small cell lung cancer with carbon-ion radiotherapy.

PubMed

Karube, Masataka; Yamamoto, Naoyoshi; Tsuji, Hiroshi; Kanematsu, Nobuyuki; Nakajima, Mio; Yamashita, Hideomi; Nakagawa, Keiichi; Kamada, Tadashi

2017-10-01

To investigate carbon-ion radiotherapy (CIRT) for in-field recurrence of stage I non-small cell lung cancer (NSCLC) initially treated with CIRT. From January 2007 to March 2014, patients initially treated for stage I NSCLC with CIRT and relapsed in-field were candidates. Overall survival (OS) rate, local control (LC) rate, progressive free survival (PFS) rate, dose to the lungs and skin, and adverse effects were analyzed. Twenty-nine patients were eligible. Median age at re-irradiation was 74years (range 53-90). Median observation period from the first day of re-irradiation was 29months (4-88months). Median prescribed dose was 46.0Gy (RBE) as initial treatment and 66.0Gy (RBE) in 12 fractions as re-irradiation. Two-year OS, LC, and PFS rates after re-irradiation were 69.0% (95% CI: 50.3-83.0), 66.9% (95% CI: 47.5-81.9), and 51.7% (95% CI: 34.1-68.9). Median skin maximum dose was 53.8Gy (RBE) (range 4.4-103.1) and median of mean lung dose was 7.3Gy (RBE) (range 2.6-14.0). There were no severer than grade 2 adverse effects except one (3.4%) grade 3 bacterial pneumonia, which was not considered radiation-induced. CIRT for stage I NSCLC local recurrence is an acceptable definitive re-treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

An open treatment trial of duloxetine in elderly patients with dysthymic disorder.

PubMed

Kerner, Nancy; D'Antonio, Kristina; Pelton, Gregory H; Salcedo, Elianny; Ferrar, Jennifer; Roose, Steven P; Devanand, Dp

2014-05-08

We evaluated the efficacy and side effects of the selective serotonin and norepinephrine reuptake inhibitor antidepressant duloxetine in older adults with dysthymic disorder. Patients ≥ 60 years old with dysthymic disorder received flexible dose duloxetine 20-120 mg daily in an open-label 12-week trial. The main outcomes were change from baseline to 12 weeks in 24-item Hamilton Depression Rating Scale scores and Treatment Emergent Symptoms Scale scores. Response required ≥ 50% decline in Hamilton Depression Rating Scale scores with a Clinical Global Impression of much improved or better, and remission required final Hamilton Depression Rating Scale ≤ 6. Intent-to-treat analyses were conducted with the last observation carried forward. In 30 patients, the mean age was 70.7 (standard deviation (SD) = 7.6) years and 56.7% were female. In intent-to-treat analyses, there were 16 responders (53.3%) and 10 remitters (33.3%). Of these, 19 patients completed the trial. The mean maximum dose was 76.3 mg (SD = 38.5) in the total sample and 101 mg (SD = 17.9) in completers. In the total sample, the mean final dose was 51 mg (SD = 27.2) and correlated significantly with decline in Hamilton Depression Rating Scale ( p < .03); decline in Hamilton Depression Rating Scale correlated significantly with decline in Treatment Emergent Symptoms Scale ( p < .001). Daily doses above 60 mg were associated with greater improvement and well tolerated. This result was partly confounded by early dropouts having received low doses. Demographic and medical comorbidities, including cardiac disease and hypertension, were not related to response. Somatic side effects were common prior to duloxetine treatment and improved rather than worsened with duloxetine. There were no serious adverse events. Duloxetine at relatively high doses showed moderate efficacy in elderly patients with dysthymic disorder and was well tolerated in successful completers. Reduced somatic symptoms were associated with improvement in depressive symptoms. A systematic placebo-controlled trial of duloxetine in older patients with dysthymic disorder may be warranted.

Dexmedetomidine inhibits activation of the MAPK pathway and protects PC12 and NG108-15 cells from lidocaine-induced cytotoxicity at its maximum safe dose.

PubMed

Wang, Qiong; Tan, Yonghong; Zhang, Na; Xu, Yingyi; Wei, Wei; She, Yingjun; Bi, Xiaobao; Zhao, Baisong; Ruan, Xiangcai

2017-07-01

The developing brains of pediatric patients are highly vulnerable to anesthetic regimen (e.g., lidocaine), potentially causing neurological impairment. Recently, dexmedetomidine (DEX) has been used as an adjunct for sedation, and was shown to exert dose-dependent neuroprotective effects during brain injury. However, the maximum safe dose of DEX is unclear, and its protective effects against lidocaine-related neurotoxicity need to be confirmed. In this study, PC12 and NG108-15 cells were used to estimate safe, non-cytotoxic doses of DEX. We found that 100 and 60μM are the maximum safe dose of DEX for PC12 and NG108-15 cells, respectively, with no significant cytotoxicity. Lidocaine was found to remarkably inhibit cell vitality, but could be reversed by different doses of DEX, especially its maximum safe dose. Furthermore, the apoptosis induced by lidocaine was also assessed, and 100 and 60μM DEX showed optimal protective effects in PC12 and NG108-15 cells, respectively. Mechanistically, DEX activated the mitogen-activated protein kinase (MAPK) pathway, impaired caspase-3 expression, and enhanced anti-apoptotic factor Bcl-2 to resist lidocaine-induced apoptosis, indicating that the optimal dose of DEX alleviates lidocaine-induced cytotoxicity and should be considered in clinical application. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Modification and validation of an analytical source model for external beam radiotherapy Monte Carlo dose calculations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Davidson, Scott E., E-mail: sedavids@utmb.edu

Purpose: A dose calculation tool, which combines the accuracy of the dose planning method (DPM) Monte Carlo code and the versatility of a practical analytical multisource model, which was previously reported has been improved and validated for the Varian 6 and 10 MV linear accelerators (linacs). The calculation tool can be used to calculate doses in advanced clinical application studies. One shortcoming of current clinical trials that report dose from patient plans is the lack of a standardized dose calculation methodology. Because commercial treatment planning systems (TPSs) have their own dose calculation algorithms and the clinical trial participant who usesmore » these systems is responsible for commissioning the beam model, variation exists in the reported calculated dose distributions. Today’s modern linac is manufactured to tight specifications so that variability within a linac model is quite low. The expectation is that a single dose calculation tool for a specific linac model can be used to accurately recalculate dose from patient plans that have been submitted to the clinical trial community from any institution. The calculation tool would provide for a more meaningful outcome analysis. Methods: The analytical source model was described by a primary point source, a secondary extra-focal source, and a contaminant electron source. Off-axis energy softening and fluence effects were also included. The additions of hyperbolic functions have been incorporated into the model to correct for the changes in output and in electron contamination with field size. A multileaf collimator (MLC) model is included to facilitate phantom and patient dose calculations. An offset to the MLC leaf positions was used to correct for the rudimentary assumed primary point source. Results: Dose calculations of the depth dose and profiles for field sizes 4 × 4 to 40 × 40 cm agree with measurement within 2% of the maximum dose or 2 mm distance to agreement (DTA) for 95% of the data points tested. The model was capable of predicting the depth of the maximum dose within 1 mm. Anthropomorphic phantom benchmark testing of modulated and patterned MLCs treatment plans showed agreement to measurement within 3% in target regions using thermoluminescent dosimeters (TLD). Using radiochromic film normalized to TLD, a gamma criteria of 3% of maximum dose and 2 mm DTA was applied with a pass rate of least 85% in the high dose, high gradient, and low dose regions. Finally, recalculations of patient plans using DPM showed good agreement relative to a commercial TPS when comparing dose volume histograms and 2D dose distributions. Conclusions: A unique analytical source model coupled to the dose planning method Monte Carlo dose calculation code has been modified and validated using basic beam data and anthropomorphic phantom measurement. While this tool can be applied in general use for a particular linac model, specifically it was developed to provide a singular methodology to independently assess treatment plan dose distributions from those clinical institutions participating in National Cancer Institute trials.« less

Study of the Emitted Dose After Two Separate Inhalations at Different Inhalation Flow Rates and Volumes and an Assessment of Aerodynamic Characteristics of Indacaterol Onbrez Breezhaler® 150 and 300 μg.

PubMed

Abadelah, Mohamad; Chrystyn, Henry; Bagherisadeghi, Golshan; Abdalla, Gaballa; Larhrib, Hassan

2018-01-01

Onbrez Breezhaler® is a low-resistance capsule-based device that was developed to deliver indacaterol maleate. The study was designed to investigate the effects of both maximum flow rate (MIF) and inhalation volume (Vin) on the dose emission of indacaterol 150 and 300 μg dose strengths after one and two inhalations using dose unit sampling apparatus (DUSA) as well as to study the aerodynamic characteristics of indacaterol Breezhaler® using the Andersen cascade impactor (ACI) at a different set of MIF and Vin. Indacaterol 150 and 300 μg contain equal amounts of lactose per carrier. However, 150 μg has the smallest carrier size. The particle size distribution (PSD) of indacaterol DPI formulations 150 and 300 μg showed that the density of fine particles increased with the increase of the primary pressure. For both strengths (150 μg and 300 μg), ED1 increased and ED2 decreased when the inhalation flow rate and inhaled volume increased. The reduction in ED1 and subsequent increase in ED2 was such that when the Vin is greater than 1 L, then 60 L/min could be regarded as the minimum MIF. The Breezhaler was effective in producing respirable particles with an MMAD ≤5 μm irrespective of the inhalation flow rate, but the mass fraction of particles with an aerodynamic diameter <3 μm is more pronounced between 60 and 90 L/min. The dose emission of indacaterol was comparable for both dose strengths 150 and 300 μg. These in vitro results suggest that a minimum MIF of 60 L/min is required during routine use of Onbrez Breezhaler®, and confirm the good practice to make two separate inhalations from the same dose.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Loupot, S; Han, T; Salehpour, M

Purpose: To quantify the difference in dose to PTV-EVAL and OARs (skin and rib) as calculated by (TG43) and heterogeneous calculations (CCC). Methods: 25 patient plans (5 Contura and 20 SAVI) were selected for analysis. Clinical dose distributions were computed with a commercially available treatment planning algorithm (TG43-D-(w,w)) and then recomputed with a pre-clinical collapsed cone convolution algorithm (CCCD-( m,m)). PTV-EVAL coverage (V90%, V95%), and rib and skin maximum dose were compared via percent difference. Differences in dose to normal tissue (V150cc, V200cc of PTV-EVAL) were also compared. Changes in coverage and maximum dose to organs at risk are reportedmore » in percent change, (100*(TG43 − CCC) / TG43)), and changes in maximum dose to normal tissue are absolute change in cc (TG43 − CCC). Results: Mean differences in V90, V95, V150, and V200 for the SAVI cases were −0.2%, −0.4%, −0.03cc, and −0.14cc, respectively, with maximum differences of −0.78%, −1.7%, 1.28cc, and 1.01cc, respectively. Mean differences in the 0.1cc dose to the rib and skin were −1.4% and −0.22%, respectively, with maximum differences of −4.5% and 16%, respectively. Mean differences in V90, V95, V150, and V200 for the Contura cases were −1.2%, −2.1%, −1.8cc, and −0.59cc, respectively, with maximum differences of −2.0%, −3.16%, −2.9cc, and −0.76cc, respectively. Mean differences in the 0.1cc dose to the rib and skin were −2.6% and −3.9%, respectively, with maximum differences of −3.2% and −5.7%, respectively. Conclusion: The effects of translating clinical knowledge based on D-(w,w) to plans reported in D-(m,m) are minimal (2% or less) on average, but vary based on the type and placement of the device, source, and heterogeneity information.« less

Effect of injected rotenone on the production and composition of urine from the rainbow trout (Salmo gairdneri)

USGS Publications Warehouse

Erickson, D.A.; Gingerich, W.H.

1986-01-01

Renal function was evaluated in adult rainbow trout (Salmo gairdneri) dosed i.a. with rotenone at 225 and 275 μg/kg. The chemical composition of urine samples and urine flow rates collected over a 5-h pretreatment period were compared with hourly urine samples collected over a 5-h posttreatment period. Significant increases in osmolality and in concentrations of sodium, potassium, chloride, glucose, and total protein were observed in the urine of treated fish. Urine solute concentrations reached maximum values within 1 to 3 h after treatment and decreased thereafter, indicating that the effects were reversible. Concentrations of sodium and chloride were highly correlated in 2-h posttreatment urine samples at the low (r = 0.922) and high (r = 0.981) rotenone treatments. Urine flow rates were reduced in trout at each dose of rotenone but the decrease in volume of urine voided was not dose-dependent. In a separate study, [14C]polyethylene glycol was used as a filtration marker to determine the effect of rotenone treatment (225 &mu:g/kg) on urine flow rate, glomerular filtration rate, and renal water reabsorption. We showed that posttreatment urine flow rates were reduced partly by reduced glomerular filtration and partly by increased water reabsorption. Transient increases in plasma osmolality and hematocrit also were observed 0.5 h after rotenone treatment.

AIR insulin capsules of different dose strengths may be combined to yield equivalent pharmacokinetics and glucodynamics.

PubMed

de la Peña, Amparo; Seger, Mary; Rave, Klaus; Heinemann, Lutz; Silverman, Bernard; Muchmore, Douglas B

2009-09-01

In order to assess pharmacokinetic (PK) and glucodynamic (GD) attributes relevant to the end user of an inhaled insulin, this study examined the exposure and GD effect of doses of AIR inhaled insulin (Eli Lilly and Co., Indianapolis, IN) (AIR is a registered trademark of Alkermes, Inc., Cambridge, MA) by combining capsules of different strengths in healthy subjects. Fifty-nine healthy, nonsmoking, male or female subjects with normal pulmonary function were enrolled in an open-label, randomized, crossover study. Subjects underwent up to five euglycemic glucose clamp procedures, separated by 5-18 days. The five AIR insulin treatments tested included one 6 unit-equivalent (U-eq) capsule containing 2.6 mg of insulin, three 2 U-eq (0.9 mg) capsules (2.7 mg total), one 10 U-eq (3.9 mg) capsule, one 6 U-eq capsule plus two 2 U-eq capsules (4.4 mg total), and two 10 U-eq capsules (7.8 mg total). Samples for PK and GD assessments were taken up to 10 h post-dose. Based on both PK (area under the curve from time 0 to time of return to baseline and maximum concentration) and GD (total amount of glucose infused and maximum glucose infusion rate) responses, administration of a 6 U-eq capsule was equivalent to three 2 U-eq capsules; 90% confidence intervals for the ratios were contained within the interval (0.8, 1.25). Similarly, both overall exposure and glucodynamic response after administration of a 10 U-eq capsule were comparable to the 6 U-eq plus two 2 U-eq capsule combination. AIR insulin exhibited PK dose proportionality and dose-dependent increases in GD responses over the 2.6-7.8 mg dose range. AIR insulin exhibited dose strength interchangeability and dose proportionality after single-dose administration in healthy subjects.

Phase I Study of Concurrent High-Dose Three-Dimensional Conformal Radiotherapy With Chemotherapy Using Cisplatin and Vinorelbine for Unresectable Stage III Non-Small-Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sekine, Ikuo, E-mail: isekine@ncc.go.jp; Sumi, Minako; Ito, Yoshinori

Purpose: To determine the maximum tolerated dose in concurrent three-dimensional conformal radiotherapy (3D-CRT) with chemotherapy for unresectable Stage III non-small-cell lung cancer (NSCLC). Patients and Methods: Eligible patients with unresectable Stage III NSCLC, age {>=}20 years, performance status 0-1, percent of volume of normal lung receiving 20 GY or more (V{sub 20}) {<=}30% received three to four cycles of cisplatin (80 mg/m{sup 2} Day 1) and vinorelbine (20 mg/m{sup 2} Days 1 and 8) repeated every 4 weeks. The doses of 3D-CRT were 66 Gy, 72 Gy, and 78 Gy at dose levels 1 to 3, respectively. Results: Of themore » 17, 16, and 24 patients assessed for eligibility, 13 (76%), 12 (75%), and 6 (25%) were enrolled at dose levels 1 to 3, respectively. The main reasons for exclusion were V{sub 20} >30% (n = 10) and overdose to the esophagus (n = 8) and brachial plexus (n = 2). There were 26 men and 5 women, with a median age of 60 years (range, 41-75). The full planned dose of radiotherapy could be administered to all the patients. Grade 3-4 neutropenia and febrile neutropenia were noted in 24 (77%) and 5 (16%) of the 31 patients, respectively. Grade 4 infection, Grade 3 esophagitis, and Grade 3 pulmonary toxicity were noted in 1 patient, 2 patients, and 1 patient, respectively. The dose-limiting toxicity was noted in 17% of the patients at each dose level. The median survival and 3-year and 4-year survival rates were 41.9 months, 72.3%, and 49.2%, respectively. Conclusions: 72 Gy was the maximum dose that could be achieved in most patients, given the predetermined normal tissue constraints.« less

Space radiation risks to the central nervous system

NASA Astrophysics Data System (ADS)

Cucinotta, Francis A.; Alp, Murat; Sulzman, Frank M.; Wang, Minli

2014-07-01

Central nervous system (CNS) risks which include during space missions and lifetime risks due to space radiation exposure are of concern for long-term exploration missions to Mars or other destinations. Possible CNS risks during a mission are altered cognitive function, including detriments in short-term memory, reduced motor function, and behavioral changes, which may affect performance and human health. The late CNS risks are possible neurological disorders such as premature aging, and Alzheimer's disease (AD) or other dementia. Radiation safety requirements are intended to prevent all clinically significant acute risks. However the definition of clinically significant CNS risks and their dependences on dose, dose-rate and radiation quality is poorly understood at this time. For late CNS effects such as increased risk of AD, the occurrence of the disease is fatal with mean time from diagnosis of early stage AD to death about 8 years. Therefore if AD risk or other late CNS risks from space radiation occur at mission relevant doses, they would naturally be included in the overall acceptable risk of exposure induced death (REID) probability for space missions. Important progress has been made in understanding CNS risks due to space radiation exposure, however in general the doses used in experimental studies have been much higher than the annual galactic cosmic ray (GCR) dose (∼0.1 Gy/y at solar maximum and ∼0.2 Gy/y at solar minimum with less than 50% from HZE particles). In this report we summarize recent space radiobiology studies of CNS effects from particle accelerators simulating space radiation using experimental models, and make a critical assessment of their relevance relative to doses and dose-rates to be incurred on a Mars mission. Prospects for understanding dose, dose-rate and radiation quality dependencies of CNS effects and extrapolation to human risk assessments are described.

SU-E-T-01: 2-D Characterization of DLG Among All MLC Leaf Pairs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumaraswamy, L; Xu, Z; Podgorsak, M

Purpose: The aim of this study is to evaluate the variation of dosimetric leaf-gap (DLG) along the travel path of each MLC leaf pair. This study evaluates whether the spatial variations in DLG could cause dose differences between TPS-calculated and measured dose. Methods: The 6MV DLG values were measured for all leaf pairs in the direction of leaf motion using a 2-D diode array and 0.6cc ion chamber. These measurements were performed on two Varian Linacs, employing the Millennium 120-leaf MLC and a 2-D-DLG variation map was created via in-house software. Several test plans were created with sweeping MLC fieldsmore » using constant gaps from 2mm to 10mm and corrected for 2-D variation utilizing in-house software. Measurements were performed utilizing the MapCHECK at 5.0cm depth for plans with and without the 2-D DLG correction and compared to the TPS calculated dose via gamma analysis (3%/3mm). Results: The measured DLGs for the middle 40 MLC leaf pairs (0.5cm width) were very similar along the central superior-inferior axis, with maximum variation of 0.2mm. The outer 20 MLC leaf pairs (1.0cm width) have DLG values from 0.32mm (mean) to 0.65mm (maximum) lower than the central leaf-pair, depending on off-axis distance. Gamma pass rates for the 2mm, 4mm, and 6mm sweep plans increased by 23.2%, 28.7%, and 26.0% respectively using the 2-D-DLG correction. The most improved dose points occur in areas modulated by the 1.0cm leaf-pairs. The gamma pass rate for the 10mm sweep plan increased by only 7.7%, indicating that the 2D variation becomes less significant for dynamic plans with larger MLC gaps. Conclusion: Fluences residing significantly off-axis with narrow sweeping gaps may exhibit significant variations from planned dose due to large differences between the true DLG exhibited by the 1.0cm leaf-pairs versus the constant DLG value utilized by the TPS for dose calculation.« less

Impact of whole brain radiation therapy on CSF penetration ability of Icotinib in EGFR-mutated non-small cell lung cancer patients with brain metastases: Results of phase I dose-escalation study.

PubMed

Zhou, Lin; He, Jiazhuo; Xiong, Weijie; Liu, Yongmei; Xiang, Jing; Yu, Qin; Liang, Maozhi; Zhou, Xiaojuan; Ding, Zhenyu; Huang, Meijuan; Ren, Li; Zhu, Jiang; Li, Lu; Hou, Mei; Ding, Lieming; Tan, Fenlai; Lu, You

2016-06-01

Whole-brain radiation therapy (WBRT) and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are both treatment options for EGFR-mutated non-small cell lung cancer (NSCLC) patients with brain metastases. However, the dose-escalation toxicity and efficacy of combination therapy, and the effect of WBRT on cerebrospinal fluid (CSF) penetration of EGFR-TKIs are still unclear. EGFR-mutated NSCLC patients with brain metastases were enrolled in this study, and the cohorts were constructed with a 3+3 design. The patients received icotinib with escalating doses (125-625mg, tid), and the concurrent WBRT (37.5Gy/15f/3weeks) started a week later. The CSF penetration rates of icotinib were tested before, immediately after, and 4 weeks after WBRT, respectively. Potential toxicities and benefits from dose-escalation treatment were analyzed. Fifteen patients were included in this study, 3 at each dose level from 125mg-375mg and 6 at 500mg with 3 occurred dose-limiting toxicities. The maximal tolerated dose of icotinib was 375mg tid in this combination therapy. There was a significant correlation between icotinib concentration in the CSF and plasma (R(2)=0.599, P<0.001). The CSF penetration rate of icotinib, from 1.2% to 9.7%, reached a maximum at 375mg (median, 6.1%). There was no significant difference for CSF penetration rates among the three test points (median, 4.1% vs. 2.8% vs. 2.8%, P=0.16). The intracranial objective response rate and median intracranial progression free survival are 80% and 18.9 months. WBRT plus concurrent icotinib is well tolerated in EGFR-mutated NSCLC patients with brain metastases, up to an icotinib dose of 375mg tid. The icotinib CSF concentration seemed to have a potential ceiling effect with the dose escalation, and WBRT seemed to have no significant impact on CSF penetration of icotinib till 4 weeks after the treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Association of malignancy with rapid growth in early lesions induced by irradiation of rat skin

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGregor, J.F.

1979-04-01

Epithelial lesions induced by irradiation of rat skin were studied to determine (a) the relationship of malignancy to dose, (b) the types of lesions and circumstances leading to overt malignancy, and (c) the growth rates of lesions progressing to malignancy versus those of lesions remaining benign. High doses of radiation were shown to be associated with the production of epidermal cancers, the maximum yield being obtained at 6,400 rads. Conversely, a peak yield of noncancerous lesions was obtained at 1,600 rads. This association between malignancy and high dose was consistent for cancers evolving from warts, cysts, and chronic ulcers. Althoughmore » the proportion of warts among the induced lesions was much higher than that of the cysts or chronic ulcers (76, 14, and 10%, respectively), the likelihood of warts becoming cancerous was substantially lower (14, 23, and 21%). The combined data for all doses showed that the latency period of the epidermal cancers was significantly (P = 0.015) shorter than that of the benign tumors. Rapid growth rates were observed for warts, cysts, and chronic ulcers progressing to overt cancer, and these did not overlap at any point on the growth scale with rates for benign tumors. This finding suggested that the potential for malignant development had been established early in the carcinogenic process, very likely at induction.« less

Kinetic modeling of simultaneous saccharification and fermentation of corn starch for ethanol production.

PubMed

Białas, Wojciech; Czerniak, Adrian; Szymanowska-Powałowska, Daria

2014-01-01

Fuel ethanol production, using a simultaneous saccharification and fermentation process (SSF) of native starch from corn flour, has been performed using Saccharomyces cerevisiae and a granular starch hydrolyzing enzyme. The quantitative effects of mash concentration, enzyme dose and pH were investigated with the use of a Box-Wilson central composite design protocol. Proceeding from results obtained in optimal fermentation conditions, a kinetics model relating the utilization rates of starch and glucose as well as the production rates of ethanol and biomass was tested. Moreover, scanning electron microscopy (SEM) was applied to investigate corn starch granule surface after the SFF process. A maximum ethanol concentration of 110.36 g/l was obtained for native corn starch using a mash concentration of 25%, which resulted in ethanol yield of 85.71%. The optimal conditions for the above yield were found with an enzyme dose of 2.05 ml/kg and pH of 5.0. These results indicate that by using a central composite design, it is possible to determine optimal values of the fermentation parameters for maximum ethanol production. The investigated kinetics model can be used to describe SSF process conducted with granular starch hydrolyzing enzymes. The SEM micrographs reveal randomly distributed holes on the surface of granules.

Range and trend of expected toxicity level (ETL) in standard A + B designs: a report from the Children's Oncology Group.

PubMed

Chen, Zhengjia; Krailo, Mark D; Sun, Junfeng; Azen, Stanley P

2009-03-01

The traditional algorithm-based 3+3 designs are most widely used for their practical simplicity in phase I clinical trials. At early stage, a common belief was that the expected toxicity level (ETL) at the maximum tolerated dose (MTD) should be 33% [Storer, B. Design and analysis of phase I clinical trials. Biometrics 1989;45;925-937, Gorden, N., Willson, J. Using toxicity grades in the design and analysis of cancer phase I clinical trials. Statistics in Medicine 1992; 11: 2063-2075, Mick, R. Phase I Clinical Trial Design. In Schilsky, R., Milano, G., Ratain, M., eds. Principles of Antineoplastic Drug Development and Pharmacology New York, NY: Marcel Dekker, 1996; 29-36]. Recently, Kang and Ahn [Kang, S., Ahn, C. The expected toxicity rate at the maximum tolerated dose in the standard phase I cancer clinical trial design. Drug Information Journal 2001; 35:1189-1199, Kang, S., Ahn, C. An investigation of the traditional algorithm-based designs for phase I cancer clinical trials. Drug Information Journal 2002; 36:865-873] found that the ETL is between 17% and 21% and He et al [He, W., Liu, J., Binkowitz, B., Quan, H. A model-based approach in the estimation of the maximum tolerated dose in phase I cancer clinical trials. Statistics in Medicine 2006; 25(12):2027-42] further reported that the ETL ranges from 19% to 24%. However they only investigated designs where the number of dose levels was at most 20. It has practical significance in designing and conducting phase I clinical trial to definitely assess the full range and trend of ETL by all possible number of tested dose levels in traditional algorithm-based A+B designs, especially 3+3 designs. In this simulation study, we originally find that the ETL decreases monotonically from about 30% to 0% as the number of dose levels increase from 3 to infinity, which will correct the inaccuracy in the common belief among phase I trial investigators. To help better design and conduct phase I trials, we create a table as a reference for the association between ETL and number of dose levels considered in a design when the exact shape of the dose-toxicity relationship is not well understood. We conclude that the number of specified dose levels is an important factor affecting substantially the ETL at MTD and recommend that fewer than 20 dose levels be designated.

A phase I trial of a new antiemetic drug--clebopride malate--in cisplatin-treated patients.

PubMed

Bleiberg, H; Piccart, M; Lips, S; Panzer, J M; N'Koua Mbon, J B

1992-02-01

Clebopride, a new benzamide derivative, has, in common with the other members of this group, antidopaminergic activity. In animals, its therapeutic ratio is superior to that of metoclopramide at doses free of side effects associated with hyperprolactinemia and extrapyramidal symptoms. The present study was designed to define the maximum tolerated dose (MTD) in patients with advanced histologically-proven cancer, treated with cisplatin at a dose of greater than 50 mg/m2. Most of them were pretreated and refractory to standard antiemetics. Clebopride was started at a dosage of 0.10 mg/kg in a group of 6 patients and escalated by 0.2 mg at each dose level. A total of 30 patients were included. Side effects include somnolence, diarrhea and extrapyramidal-like symptoms. The latter occurred at almost all dose levels in 14% of the cycles and limited continuation of the study. Activity in this group of patients was encouraging but, considering the rate of extrapyramidal symptoms, further dose escalation is not indicated and activity at lower, nontoxic levels should be investigated.

Thermoluminescence dosimetry for in-vivo verification of high dose rate brachytherapy for prostate cancer.

PubMed

Das, R; Toye, W; Kron, T; Williams, S; Duchesne, G

2007-09-01

It was the aim of the study to verify dose delivered in urethra and rectum during High Dose Rate brachytherapy boost (HDRBB) of prostate cancer patients. During the first fraction of HDRBB measurement catheters were placed in the urethra and rectum of prostate cancer patients. These contained LiF:Mg,Ti Thermoluminescence Dosimetry (TLD) rods of 1 mm diameter, with up to 11 detectors positioned every 16 mm separated by radio-opaque markers. A Lorentzian peak function was used to fit the data. Measurements from 50 patients were evaluated and measured doses were compared with predictions from the treatment planning system (Plato Vs 13.5 to 14.1). Prospective urinary and rectal toxicity scores were collected following treatment. In more than 90% of cases, the Lorentzian peak function provided a good fit to both experimental and planning urethral data (r2 > 0.9). In general there was good agreement between measured and predicted doses with the average difference between measured and planned maximum dose being 0.1 Gy. No significant association between dose and any clinical endpoints was observed in 43 patients available for clinical evaluation. An average inferior shift of 2 mm between the plan and the measurement performed approximately 1 hour after the planning CT scan was found for the dose distribution in the cohort of patients for the urethra measurements. Rectal measurements proved to be more difficult to interpret as there is more variability of TLD position between planning and treatment. TLD in-vivo measurements are easily performed in urethra and rectum during HDR brachytherapy of prostate patients. They verify the delivery and provide information about the dose delivered to critical structures. The latter may be of particular interest if higher doses are to be given per fraction such as in HDR monotherapy.

Medium doses of daily vitamin D decrease falls and higher doses of daily vitamin D3 increase falls: A randomized clinical trial.

PubMed

Smith, Lynette M; Gallagher, J Christopher; Suiter, Corinna

2017-10-01

Falls are a serious health problem in the aging population. Because low levels of vitamin D have been associated with increased fall rates, many trials have been performed with vitamin D; two meta-analyses showed either a small effect or no effect of vitamin D on falls. We conducted a study of the effect of vitamin D on serum 25 hydroxyvitamin D (25OHD) and data on falls was collected as a secondary outcome. In a 12-month double blind randomized placebo trial, elderly women, mean age 66 years, were randomized to one of seven daily oral doses of vitamin D or placebo. The main inclusion criterion for study was a baseline serum 25OHD<20ng/ml (50nmol/L). A history of falls was collected at baseline and fall events were collected every 3 months. Results showed that the effect of vitamin D on falls followed a U-shaped curve whether analyzed by dose or serum 25OHD levels. There was no decrease in falls on low vitamin D doses 400, 800 IU, a significant decrease on medium doses 1600, 2400,3200 IU (p=0.020) and no decrease on high doses 4000, 4800 IU compared to placebo (p=0.55). When compared to 12-month serum 25OHD quintiles, the faller rate was 60% in the lowest quintile <25ng/ml (<50nmol/L), 21% in the low middle quintile 32-38ng/ml (80-95nmo/L), 72% in the high middle quintile 38-46ng/ml (95-115nmo/L) and 45% in the highest quintile 46-66ng/ml (115-165nmol/L). In the subgroup with a fall history, fall rates were 68% on low dose, 27% on medium doses and 100% on higher doses. Fall rates on high doses were increased compared to medium doses (Odds Ratio 5.6.95% CI: 2.1-14.8). In summary, the maximum decrease in falls corresponds to a 12- month serum 25OHD of 32-38ng/ml (80-95nmol/L) and faller rates increase as serum 25OHD exceed 40-45ng/ml (100-112.5nmol/L). The Tolerable upper limit (TUL) recently increased in 2010 from 2000 to 4000 IU/day may need to be reduced in elderly women especially in those with a fall history. Copyright © 2017 Elsevier Ltd. All rights reserved.

SU-E-T-795: Validations of Dose Calculation Accuracy of Acuros BV in High-Dose-Rate (HDR) Brachytherapy with a Shielded Cylinder Applicator Using Monte Carlo Simulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Y; Department of Engineering Physics, Tsinghua University, Beijing; Tian, Z

Purpose: Acuros BV has become available to perform accurate dose calculations in high-dose-rate (HDR) brachytherapy with phantom heterogeneity considered by solving the Boltzmann transport equation. In this work, we performed validation studies regarding the dose calculation accuracy of Acuros BV in cases with a shielded cylinder applicator using Monte Carlo (MC) simulations. Methods: Fifteen cases were considered in our studies, covering five different diameters of the applicator and three different shielding degrees. For each case, a digital phantom was created in Varian BrachyVision with the cylinder applicator inserted in the middle of a large water phantom. A treatment plan withmore » eight dwell positions was generated for these fifteen cases. Dose calculations were performed with Acuros BV. We then generated a voxelized phantom of the same geometry, and the materials were modeled according to the vendor’s specifications. MC dose calculations were then performed using our in-house developed fast MC dose engine for HDR brachytherapy (gBMC) on a GPU platform, which is able to simulate both photon transport and electron transport in a voxelized geometry. A phase-space file for the Ir-192 HDR source was used as a source model for MC simulations. Results: Satisfactory agreements between the dose distributions calculated by Acuros BV and those calculated by gBMC were observed in all cases. Quantitatively, we computed point-wise dose difference within the region that receives a dose higher than 10% of the reference dose, defined to be the dose at 5mm outward away from the applicator surface. The mean dose difference was ∼0.45%–0.51% and the 95-percentile maximum difference was ∼1.24%–1.47%. Conclusion: Acuros BV is able to accurately perform dose calculations in HDR brachytherapy with a shielded cylinder applicator.« less

Dosimetry of intracavitary placements for uterine and cervical carcinoma: results of orthogonal film, TLD, and CT-assisted techniques.

PubMed

Kapp, K S; Stuecklschweiger, G F; Kapp, D S; Hackl, A G

1992-07-01

A total of 720 192Ir high-dose-rate (HDR) applications in 331 patients with gynecological tumors were analyzed to evaluate the dose to normal tissues from brachytherapy. Based on the calculations of bladder base, bladder neck, and rectal doses derived from orthogonal films the planned tumor dose or fractionation was altered in 20.4% of intracavitary placements (ICP) for cervix carcinoma and 9.2% of ICP for treatment of the vaginal vault. In 13.8% of intracervical and 8.1% of intravaginal treatments calculated doses to both the bladder and rectum were greater than or equal to 140% of the initially planned dose fraction. Doses at the bladder base were significantly higher than at the bladder neck (p less than 0.001). In 17.5% of ICP the dose to the bladder base was at least twice as high as to the bladder neck. The ratio of bladder base dose to the bladder neck was 1.5 (+/- 1.19 SD) for intracervical and 1.46 (+/- 1.14 SD) for intravaginal applications. The comparison of calculated doses from orthogonal films with in-vivo readings showed a good correlation of rectal doses with a correlation coefficient factor of 0.9556. CT-assisted dosimetry, however, revealed that the maximum doses to bladder and rectum were generally higher than those obtained from films with ratios of 1-1.7 (average: 1.44) for the bladder neck, 1-5.4 (average: 2.42) for the bladder base, and 1.1-2.7 (average: 1.37) for the rectum. When doses to the specified reference points of bladder neck and rectum from orthogonal film dosimetry were compared with the corresponding points on CT scans, similar values were obtained for both methods with a maximum deviation of +/- 10%. Despite the determination of multiple reference points our study revealed that this information was inadequate to predict doses to the entire rectum and bladder. If conventional methods are used for dosimetry it is recommended that doses to the bladder base should be routinely calculated, since single point measurements at the bladder neck seriously underestimate the dose to the bladder. Also the rectal dose should be determined at several points over the length of the implant due to the wide range of anatomic variations possible.

Lhermitte Sign After Chemo-IMRT of Head-and-Neck Cancer: Incidence, Doses, and Potential Mechanisms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pak, Daniel; Vineberg, Karen; Feng, Felix

2012-08-01

Purpose: We have observed a higher rate of Lhermitte sign (LS) after chemo-intensity-modulated radiotherapy (IMRT) of head-and-neck cancer than the published rates after conventional radiotherapy. We hypothesized that the inhomogeneous spinal cord dose distributions produced by IMRT caused a 'bath-and-shower' effect, characterized by low doses in the vicinity of high doses, reducing spinal cord tolerance. Methods and Materials: Seventy-three patients with squamous cell carcinoma of the oropharynx participated in a prospective study of IMRT concurrent with weekly carboplatin and paclitaxel. Of these, 15 (21%) reported LS during at least 2 consecutive follow-up visits. Mean dose, maximum dose, and partial volumemore » and absolute volume (in milliliters) of spinal cord receiving specified doses ({>=}10 Gy, {>=}20 Gy, {>=}30 Gy, and {>=}40 Gy), as well as the pattern of dose distributions at the 'anatomic' spinal cord (from the base of the skull to the aortic arch) and 'plan-related' spinal cord (from the top through the bottom of the planning target volumes), were compared between LS patients and 34 non-LS patients. Results: LS patients had significantly higher spinal cord mean doses, V{sub 30}, V{sub 40}, and absolute volumes receiving 30 Gy or more and 40 Gy or more compared with the non-LS patients (p < 0.05). The strongest predictors of LS were higher V{sub 40} and higher cord volumes receiving 40 Gy or more (p {<=} 0.007). There was no evidence of larger spinal cord volumes receiving low doses in the vicinity of higher doses (bath-and-shower effect) in LS compared with non-LS patients. Conclusions: Greater mean dose, V{sub 30}, V{sub 40}, and cord volumes receiving 30 Gy or more and 40 Gy or more characterized LS compared with non-LS patients. Bath-and-shower effects could not be validated in this study as a potential contributor to LS. The higher-than-expected rates of LS may be because of the specific concurrent chemotherapy agents or more accurate identification of LS in the setting of a prospective study.« less

Individual differences in the reinforcing and punishing effects of nicotine in rhesus monkeys.

PubMed

Koffarnus, Mikhail N; Winger, Gail

2015-07-01

The relatively weak reinforcing effects of nicotine in experimental studies have been attributed to possible aversive effects or the need to space nicotine administrations over time to expose reinforcing effects. This study was designed to determine if the response-maintaining effects of nicotine are increased when availability is spaced through time, and whether nicotine is an effective punisher of remifentanil-maintained responding. Compared to a cocaine reference dose, nicotine dose and timeout (TO) value were varied in eight rhesus monkeys responding for intravenous (i.v.) nicotine on varying fixed-ratio (FR) schedules of reinforcement.The aversive effects of nicotine were evaluated in four animals choosing between a standard dose of remifentanil alone or in combination with one of several doses of nicotine. In three of eight self-administration monkeys, 0.01 mg/kg/inj nicotine did not maintain responding at any FR value. In the other five animals, nicotine-maintained response rates increased with either FR or TO values to a certain point, and then slowed. Maximum nicotine-maintained response rates were much slower than those maintained by cocaine, and demand for nicotine was less than demand for cocaine. Nicotine was an effective punisher of remifentanil-maintained responding at doses ranging from 0.01 to 0.3 mg/kg/inj. Lower punishing dose seemed to be related to the absence of reinforcing effects within subject. There are an order of magnitude individual differences in sensitivity to both the reinforcing and punishing effects of nicotine, and this drug may be unique in being a weak positive reinforcer in small doses and aversive in large doses.

SU-E-I-31: Differences Observed in Radiation Doses Across 2 Similar CT Scanners From Adult Brain-Neck CT Angiography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fujii, K; UCLA School of Medicine, Los Angeles, CA; McMillan, K

2015-06-15

Purpose: The aim of this study is to evaluate the difference in radiation doses from adult Brain-Neck CT angiography (CTA) between two CT scanners. Methods: We collected CT dose index data (CTDIvol, DLP) from adult Brain-Neck CTA performed with two CT scanners (Sensation 64 (S64) and Definition AS (AS), Siemens Healthcare) performed at two of our facilities from Jan 1st to Dec 31th, 2014. X-ray dose management software (Radmetrics, Bayer Healthcare) was used to mine these data. All exams were performed with Tube Current Modulation (Care Dose 4D), tube voltage of 120 kVp, quality reference mAs of 300, beam collimationmore » of 64*0.6 mm. The rotation time was set to 0.5 sec for S64 and 1.0 sec for AS. We also scanned an anthropomorphic skull and chest phantom under routine Brain-Neck CTA protocol with the two scanners and extracted the tube current values from the raw projection data. Results: The mean CTDIvol and DLP in Brain-Neck CTA was 72 mGy and 2554 mGy*cm for AS, which was substantially larger than the mean values of 46 mGy and 1699 mGy*cm for S64. The maximum tube current was 583 mA for most cases on the S64 while the maximum was 666 mA for AS even though the rotation time set for AS was 1.0 sec. Measurements obtained with the anthropomorphic phantom showed that the tube current reached 583 mA at the shoulder region for S64 while it reached to 666 mA for AS. Conclusion: The results of this study showed that substantially different CT doses can Result from Brain-Neck CTA protocols even when similar scanners and similar settings are used. Though both scanners have a similar maximum mA rating, differences in mA were observed through the shoulders, resulting in substantially different CTDIvol values.« less

The Fukushima Health Management Survey: estimation of external doses to residents in Fukushima Prefecture

NASA Astrophysics Data System (ADS)

Ishikawa, Tetsuo; Yasumura, Seiji; Ozasa, Kotaro; Kobashi, Gen; Yasuda, Hiroshi; Miyazaki, Makoto; Akahane, Keiichi; Yonai, Shunsuke; Ohtsuru, Akira; Sakai, Akira; Sakata, Ritsu; Kamiya, Kenji; Abe, Masafumi

2015-08-01

The Fukushima Health Management Survey (including the Basic Survey for external dose estimation and four detailed surveys) was launched after the Fukushima Dai-ichi Nuclear Power Plant accident. The Basic Survey consists of a questionnaire that asks Fukushima Prefecture residents about their behavior in the first four months after the accident; and responses to the questionnaire have been returned from many residents. The individual external doses are estimated by using digitized behavior data and a computer program that included daily gamma ray dose rate maps drawn after the accident. The individual external doses of 421,394 residents for the first four months (excluding radiation workers) had a distribution as follows: 62.0%, <1 mSv 94.0%, <2 mSv 99.4%, <3 mSv. The arithmetic mean and maximum for the individual external doses were 0.8 and 25 mSv, respectively. While most dose estimation studies were based on typical scenarios of evacuation and time spent inside/outside, the Basic Survey estimated doses considering individually different personal behaviors. Thus, doses for some individuals who did not follow typical scenarios could be revealed. Even considering such extreme cases, the estimated external doses were generally low and no discernible increased incidence of radiation-related health effects is expected.

The Fukushima Health Management Survey: estimation of external doses to residents in Fukushima Prefecture

PubMed Central

Ishikawa, Tetsuo; Yasumura, Seiji; Ozasa, Kotaro; Kobashi, Gen; Yasuda, Hiroshi; Miyazaki, Makoto; Akahane, Keiichi; Yonai, Shunsuke; Ohtsuru, Akira; Sakai, Akira; Sakata, Ritsu; Kamiya, Kenji; Abe, Masafumi

2015-01-01

The Fukushima Health Management Survey (including the Basic Survey for external dose estimation and four detailed surveys) was launched after the Fukushima Dai-ichi Nuclear Power Plant accident. The Basic Survey consists of a questionnaire that asks Fukushima Prefecture residents about their behavior in the first four months after the accident; and responses to the questionnaire have been returned from many residents. The individual external doses are estimated by using digitized behavior data and a computer program that included daily gamma ray dose rate maps drawn after the accident. The individual external doses of 421,394 residents for the first four months (excluding radiation workers) had a distribution as follows: 62.0%, <1 mSv; 94.0%, <2 mSv; 99.4%, <3 mSv. The arithmetic mean and maximum for the individual external doses were 0.8 and 25 mSv, respectively. While most dose estimation studies were based on typical scenarios of evacuation and time spent inside/outside, the Basic Survey estimated doses considering individually different personal behaviors. Thus, doses for some individuals who did not follow typical scenarios could be revealed. Even considering such extreme cases, the estimated external doses were generally low and no discernible increased incidence of radiation-related health effects is expected. PMID:26239643

Computer calculated dose in paediatric prescribing.

PubMed

Kirk, Richard C; Li-Meng Goh, Denise; Packia, Jeya; Min Kam, Huey; Ong, Benjamin K C

2005-01-01

Medication errors are an important cause of hospital-based morbidity and mortality. However, only a few medication error studies have been conducted in children. These have mainly quantified errors in the inpatient setting; there is very little data available on paediatric outpatient and emergency department medication errors and none on discharge medication. This deficiency is of concern because medication errors are more common in children and it has been suggested that the risk of an adverse drug event as a consequence of a medication error is higher in children than in adults. The aims of this study were to assess the rate of medication errors in predominantly ambulatory paediatric patients and the effect of computer calculated doses on medication error rates of two commonly prescribed drugs. This was a prospective cohort study performed in a paediatric unit in a university teaching hospital between March 2003 and August 2003. The hospital's existing computer clinical decision support system was modified so that doctors could choose the traditional prescription method or the enhanced method of computer calculated dose when prescribing paracetamol (acetaminophen) or promethazine. All prescriptions issued to children (<16 years of age) at the outpatient clinic, emergency department and at discharge from the inpatient service were analysed. A medication error was defined as to have occurred if there was an underdose (below the agreed value), an overdose (above the agreed value), no frequency of administration specified, no dose given or excessive total daily dose. The medication error rates and the factors influencing medication error rates were determined using SPSS version 12. From March to August 2003, 4281 prescriptions were issued. Seven prescriptions (0.16%) were excluded, hence 4274 prescriptions were analysed. Most prescriptions were issued by paediatricians (including neonatologists and paediatric surgeons) and/or junior doctors. The error rate in the children's emergency department was 15.7%, for outpatients was 21.5% and for discharge medication was 23.6%. Most errors were the result of an underdose (64%; 536/833). The computer calculated dose error rate was 12.6% compared with the traditional prescription error rate of 28.2%. Logistical regression analysis showed that computer calculated dose was an important and independent variable influencing the error rate (adjusted relative risk = 0.436, 95% CI 0.336, 0.520, p < 0.001). Other important independent variables were seniority and paediatric training of the person prescribing and the type of drug prescribed. Medication error, especially underdose, is common in outpatient, emergency department and discharge prescriptions. Computer calculated doses can significantly reduce errors, but other risk factors have to be concurrently addressed to achieve maximum benefit.

The effect of oral contraceptive steroids on bile secretion and bilirubin Tm in rats

PubMed Central

Heikel, T. A. J.; Lathe, G. H.

1970-01-01

1. The effect of oestrogens and progestogens and their 17α-ethinyl derivatives on bile flow, maximum rate of bilirubin secretion, serum and liver bilirubin has been studied. 2. Both 17α-ethinyl substituted oestrogens and progestogens greatly reduced the basal bile flow. The parent compounds, oestradiol-17β and 19-nortestosterone had little or no effect. 3. A much larger dose of progestogens (40 mg/kg) than oestrogens (5 mg/kg) was needed. 4. Between 12 and 48 h were required for 17α-ethinyloestradiol to produce the effect. 5. Bilirubin maximum secretion rate (Tm) was little affected, the only significant reduction being produced by the 3-methyl ether of 17α-ethinyloestradiol (mestranol). 6. Rises in serum conjugated bilirubin following infusion of bilirubin were produced by 17α-ethinyloestradiol and mestranol but not by the progestogens. PMID:5441412

Natural radioactivity and radon exhalation rates in man-made tiles used as building materials in Japan.

PubMed

Iwaoka, K; Hosoda, M; Suwankot, N; Omori, Y; Ishikawa, T; Yonehara, H; Tokonami, S

2015-11-01

Man-made tiles frequently used in Japan were collected, and activity concentrations and radon ((222)Rn) exhalation rates in these tiles were measured. Dose estimations for inhabitants living in houses built using these tiles were also carried out. The activity concentrations of (226)Ra, (228)Ra and (40)K in the man-made tiles were 31-170, 35-110 and 260-980 Bq kg(-1), respectively. The (222)Rn exhalation rates in the tiles were 8.8-21 μBq m(-2) s(-1). The ranges of experimental activity concentrations and (222)Rn exhalation rates were almost identical to those of natural rocks used as typical building materials in Japan. The maximum value of effective dose to inhabitants living in houses built with the man-made tiles was 0.14 mSv y(-1), which is lower than the reference level range (1-20 mSv y(-1)) for abnormally high levels of natural background radiation published in the ICRP Publication 103. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Brachial Plexus-Associated Neuropathy After High-Dose Radiation Therapy for Head-and-Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Allen M., E-mail: allen.chen@ucdmc.ucdavis.edu; Hall, William H.; Li, Judy

2012-09-01

Purpose: To identify clinical and treatment-related predictors of brachial plexus-associated neuropathies after radiation therapy for head-and-neck cancer. Methods and Materials: Three hundred thirty patients who had previously completed radiation therapy for head-and-neck cancer were prospectively screened using a standardized instrument for symptoms of neuropathy thought to be related to brachial plexus injury. All patients were disease-free at the time of screening. The median time from completion of radiation therapy was 56 months (range, 6-135 months). One-hundred fifty-five patients (47%) were treated by definitive radiation therapy, and 175 (53%) were treated postoperatively. Radiation doses ranged from 50 to 74 Gy (median,more » 66 Gy). Intensity-modulated radiation therapy was used in 62% of cases, and 133 patients (40%) received concurrent chemotherapy. Results: Forty patients (12%) reported neuropathic symptoms, with the most common being ipsilateral pain (50%), numbness/tingling (40%), motor weakness, and/or muscle atrophy (25%). When patients with <5 years of follow-up were excluded, the rate of positive symptoms increased to 22%. On univariate analysis, the following factors were significantly associated with brachial plexus symptoms: prior neck dissection (p = 0.01), concurrent chemotherapy (p = 0.01), and radiation maximum dose (p < 0.001). Cox regression analysis confirmed that both neck dissection (p < 0.001) and radiation maximum dose (p < 0.001) were independently predictive of symptoms. Conclusion: The incidence of brachial plexus-associated neuropathies after radiation therapy for head-and-neck cancer may be underreported. In view of the dose-response relationship identified, limiting radiation dose to the brachial plexus should be considered when possible.« less

A population pharmacokinetic model of AT9283 in adults and children to predict the maximum tolerated dose in children with leukaemia.

PubMed

Duong, Janna K; Griffin, Melanie J; Hargrave, Darren; Vormoor, Josef; Edwards, David; Boddy, Alan V

2017-08-01

AT9283 is used to treat patients with solid tumours and patients with leukaemia. However, the maximum tolerated dose (MTD) for children with leukaemia remains unknown due to early termination of the Phase I trial. The aim of this study was to develop a population model of AT9283 to describe the pharmacokinetics in adults and children and to estimate the MTD in children with leukaemia. Data from Phase I dose-escalation studies in adults and children were used to build a population pharmacokinetic model (NONMEM v7.3). Potential covariates investigated included body weight, body surface area (BSA), glomerular filtration rate (GFR), age and sex. Model-derived area under the concentration-time curve was used to investigate the relationship between dose and exposure in adults and children. The plasma concentrations of AT9283 (n = 1770) from 92 patients (53 adults, 39 children) were used to build a two-compartment model with all pharmacokinetic parameters scaled using body weight. Renal function (GFR), but not BSA, was a significant covariate for the clearance of AT9283. In children with leukaemia (median weight 16 kg), a flat dose of 500 mg 72 h -1 provided similar drug exposures at the MTD as the adult population. The estimated MTD for children with leukaemia, therefore, is 30 mg kg -1  72 h -1 . For adults, GFR was a significant predictor of clearance, whilst body-weight based dosing was more useful than BSA in determining the drug exposure in children. The MTD was estimated to be 30 mg kg -1  72 h -1 children with leukaemia. © 2017 The British Pharmacological Society.

Dosimetric impact of an air passage on intraluminal brachytherapy for bronchus cancer

PubMed Central

Okamoto, Hiroyuki; Wakita, Akihisa; Nakamura, Satoshi; Nishioka, Shie; Aikawa, Ako; Kato, Toru; Abe, Yoshihisa; Kobayashi, Kazuma; Inaba, Koji; Murakami, Naoya; Itami, Jun

2016-01-01

The brachytherapy dose calculations used in treatment planning systems (TPSs) have conventionally been performed assuming homogeneous water. Using measurements and a Monte Carlo simulation, we evaluated the dosimetric impact of an air passage on brachytherapy for bronchus cancer. To obtain the geometrical characteristics of an air passage, we analyzed the anatomical information from CT images of patients who underwent intraluminal brachytherapy using a high-dose-rate 192Ir source (MicroSelectron V2r®, Nucletron). Using an ionization chamber, we developed a measurement system capable of measuring the peripheral dose with or without an air cavity surrounding the catheter. Air cavities of five different radii (0.3, 0.5, 0.75, 1.25 and 1.5 cm) were modeled by cylindrical tubes surrounding the catheter. A Monte Carlo code (GEANT4) was also used to evaluate the dosimetric impact of the air cavity. Compared with dose calculations in homogeneous water, the measurements and GEANT4 indicated a maximum overdose of 5–8% near the surface of the air cavity (with the maximum radius of 1.5 cm). Conversely, they indicated a minimum overdose of ~1% in the region 3–5 cm from the cavity surface for the smallest radius of 0.3 cm. The dosimetric impact depended on the size and the distance of the air passage, as well as the length of the treatment region. Based on dose calculations in water, the TPS for intraluminal brachytherapy for bronchus cancer had an unexpected overdose of 3–5% for a mean radius of 0.75 cm. This study indicates the need for improvement in dose calculation accuracy with respect to intraluminal brachytherapy for bronchus cancer. PMID:27605630

Phase I Trial Using Induction Ciplatin, Docetaxel, 5-FU and Erlotinib Followed by Cisplatin, Bevacizumab and Erlotinib With Concurrent Radiotherapy for Advanced Head and Neck Cancer.

PubMed

Ahn, Peter H; Machtay, Mitchell; Anne, Pramila R; Cognetti, David; Keane, William M; Wuthrick, Evan; Dicker, Adam P; Axelrod, Rita S

2018-05-01

Bevacizumab (avastin) and erlotinib (tarceva) had shown early clinical activity against head and neck cancer (HNC). We initiated a phase I trial of induction cisplatin, docetaxel, 5-fluorouracil and erlotinib (TPF-E) followed by cisplatin, bevacizumab and erlotinib (PA-E) with radiotherapy (XRT) for advanced HNC. The goal was to determine maximum tolerated erlotinib dose. Eligible patients had stage IVA or higher HNC with good performance status, hematologic, and renal reserve. Two cycles of induction TPF-E were administered. XRT was administered with concurrent weekly cisplatin and bevacizumab every 2 weeks. Initial erlotinib dose was 50 mg daily from start of induction chemotherapy until radiotherapy completion. Erlotinib dose escalations to 100 and 150 mg were planned. Thirteen patients with previously untreated locoregional disease (11 patients) or oligometastatic (2 patients) HNC were enrolled. Totally, 11 of 13 patients completed XRT as planned. Four of 8 patients in cohort 1 (erlotinib 50 mg), 3 of 4 patients in cohort 2 (100 mg), and 0 of 1 patients in cohort 3 (150 mg) completed the regimen. Two patients had significant gastrointestinal complications (bleeding and perforation), and 1 had dose-limiting diarrhea. Maximum tolerated dose was reached at 50 mg erlotinib. At median 23.4 months follow-up, 5 patients (38%) have no evidence of disease, and 2 (15%) have stable but measurable disease. Erlotinib in combination with induction TPF followed by erlotinib, cisplatin, and bevacizumab with XRT is active but toxic. Gastrointestinal toxicities partly caused high rates of study withdrawal. All doses studied in this protocol caused unexpected toxicities and we do not recommend advancement to phase II.

Survey of Occupational Noise Exposure in CF Personnel in Selected High-Risk Trades

DTIC Science & Technology

2003-11-01

peak, maximum level , minimum level , average sound level , time weighted average, dose, projected 8-hour dose, and upper limit time were measured for...10 4.4.2 Maximum Sound Level ...11 4.4.3 Minimum Sound Level

Dose-finding study of intensive weekly alternating schedule of docetaxel, 5-fluorouracil, and oxaliplatin, FD/FOx regimen, in metastatic gastric cancer.

PubMed

Bruera, Gemma; Massacese, Silvia; Galvano, Antonio; Mas, Antonella Dal; Guadagni, Stefano; Calvisi, Giuseppe; Ciacco, Eugenio; Russo, Antonio; Ricevuto, Enrico

2018-04-17

Proper administration timing, dose-intensity, efficacy/toxicity ratio of triplet docetaxel (DTX), 5-fluorouracil (5-FU), and oxaliplatin (OXP) should be improved to safely perform three-drugs intensive first line in advanced gastric cancer (GC). This dose-finding study investigated recommended 5-FU and OXP doses, safety of triplet regimen and preliminary activity. Schedule: 12h-timed-flat-infusion 5-FU 700-1000 mg/m 2 /d 1-2, 8-9, 15-16, 22-23, with 100 mg/m 2 /d increase for dose level; DTX 50 mg/m 2 d 1, 15 fixed dose, OXP at three increasing dose-levels 60-70-80 mg/m 2 d 8, 22, every 4 weeks. Intra- and inter-patients dose-escalation was planned. Ten fit <75 years patients were enrolled: median age 59; young-elderly 4 (40%). From first to fifth dose level, 5 patients (1 per cohort) were enrolled according to intra-patient dose escalation, no dose-limiting toxicity (DLT) were reported. At sixth level, 1 DLT, G2 diarrhea, was reported, thus other 2 patients were enrolled, DLT 1/3 patients (33%). Maximum tolerated dose (MTD) was not reached. 5-FU and OXP recommended doses (RD) were 1000 mg/m 2 /d and 80 mg/m 2 , respectively. To confirm RD, other 3 patients were enrolled, without DLT. Cumulative G3-4 toxicities were: neutropenia 50%, leucopenia 20%, hypoalbuminemia 10%, mucositis 10%, asthenia 20%. Limiting toxicity syndromes were 30%, 25% in young-elderly, all multiple site. Objective response rate intent-to-treat 60%, disease control rate 90%. After 15 months follow-up, progression-free and overall survival, 6 and 17 months, respectively. First line intensive FD/FOx regimen adding DXT/5-FU/OXP can be safely administered at recommended doses in advanced GC, with promising high activity and efficacy.

Inhibitory effects of Enteromorpha linza polysaccharide on micronucleus of Allium sativum root cells.

PubMed

Zhang, Zhongshan; Wang, Xiaomei; Li, Jingfen; Liu, Chongbin; Zhang, Quanbin

2016-06-01

In this study, the antimutagenic function of the polysaccharide from Enteromorpha linza with the micronucleus test of Allium sativum root cells induced by sulfur dioxide and ultraviolet was studied. The concentration-effect relation of the two inducers was firstly evaluated. The results showed that an increase of genotoxicity damage was demonstrated and micronuclei frequency induced by sulfur dioxide and ultraviolet displayed dose dependent increases. All the doses of polysaccharide did affect the micronuclei frequency formation compared with the negative control. And also, the significant increase in inhibition rate of micronuclei frequency was observed with the increase of the dose of polysaccharide. It was showed maximum inhibition of micronuclei frequency cells (71.74% and 66.70%) at a concentration of 200g/mL in three experiments. The low molecular weight polysaccharide showed higher inhibition rate than raw polysaccharide at the higher concentration (50g/mL) in the absence of sulfur dioxide and ultraviolet. It was confirmed to be a good mutant inhibitor. Copyright © 2016 Elsevier B.V. All rights reserved.

Electron fluence correction factors for various materials in clinical electron beams.

PubMed

Olivares, M; DeBlois, F; Podgorsak, E B; Seuntjens, J P

2001-08-01

Relative to solid water, electron fluence correction factors at the depth of dose maximum in bone, lung, aluminum, and copper for nominal electron beam energies of 9 MeV and 15 MeV of the Clinac 18 accelerator have been determined experimentally and by Monte Carlo calculation. Thermoluminescent dosimeters were used to measure depth doses in these materials. The measured relative dose at dmax in the various materials versus that of solid water, when irradiated with the same number of monitor units, has been used to calculate the ratio of electron fluence for the various materials to that of solid water. The beams of the Clinac 18 were fully characterized using the EGS4/BEAM system. EGSnrc with the relativistic spin option turned on was used to optimize the primary electron energy at the exit window, and to calculate depth doses in the five phantom materials using the optimized phase-space data. Normalizing all depth doses to the dose maximum in solid water stopping power ratio corrected, measured depth doses and calculated depth doses differ by less than +/- 1% at the depth of dose maximum and by less than 4% elsewhere. Monte Carlo calculated ratios of doses in each material to dose in LiF were used to convert the TLD measurements at the dose maximum into dose at the center of the TLD in the phantom material. Fluence perturbation correction factors for a LiF TLD at the depth of dose maximum deduced from these calculations amount to less than 1% for 0.15 mm thick TLDs in low Z materials and are between 1% and 3% for TLDs in Al and Cu phantoms. Electron fluence ratios of the studied materials relative to solid water vary between 0.83+/-0.01 and 1.55+/-0.02 for materials varying in density from 0.27 g/cm3 (lung) to 8.96 g/cm3 (Cu). The difference in electron fluence ratios derived from measurements and calculations ranges from -1.6% to +0.2% at 9 MeV and from -1.9% to +0.2% at 15 MeV and is not significant at the 1sigma level. Excluding the data for Cu, electron fluence correction factors for open electron beams are approximately proportional to the electron density of the phantom material and only weakly dependent on electron beam energy.

A Phase I study of bizelesin (NSC 615291) in patients with advanced solid tumors.

PubMed

Pitot, Henry C; Reid, Joel M; Sloan, Jeff A; Ames, Matthew M; Adjei, Alex A; Rubin, Joseph; Bagniewski, Pamela G; Atherton, Pamela; Rayson, Daniel; Goldberg, Richard M; Erlichman, Charles

2002-03-01

To evaluate the toxicities, characterize the pharmacokinetics, and determine the maximum-tolerated dose of bizelesin administered once every 4 weeks. Patients with advanced solid tumors received escalating doses of bizelesin as an i.v. push every 4 weeks. Pharmacokinetic studies were performed with the first treatment cycle. Nineteen eligible patients received a total of 54 courses of bizelesin at doses ranging from 0.1 to 1 microg/m(2). Dose-limiting toxicity of neutropenia was seen in 2 of 4 patients treated at the 1 microg/m(2) dose level. Nonhematological toxicity was generally mild with maximum toxicity being

Radiation synthesis and characterization of hyaluronan capped gold nanoparticles.

PubMed

Hien, Nguyen Quoc; Van Phu, Dang; Duy, Nguyen Ngoc; Quoc, Le Anh

2012-06-20

Gold nanoparticles (AuNPs) with diameter from 4 to 10nm, capping by hyaluronan (HA) were synthesized using a γ-irradiation method. The maximum absorption wavelengths at 517-525 nm of colloidal AuNPs/HA solutions were measured by UV-vis spectroscopy. The size and size distribution of AuNPs were determined from TEM images. The influence of various factors on the size of AuNPs particularly the concentration of Au3+ and HA, and dose rate were also investigated. Results indicated that higher dose rate and HA concentration favor smaller sizes of AuNPs whereas the size increases with Au3+ concentration. The colloidal AuNPs/HA solution was fairly stable more than 6 months under storage at ambient condition. The AuNPs stabilized by biocompatible HA with the size less than 10nm as prepared can potentially be applied in biomedicines and cosmetics. Copyright © 2012 Elsevier Ltd. All rights reserved.

Assessment of Intervention by a Palliative Care Team Working in a Japanese General Hospital: A Retrospective Study.

PubMed

Amano, Koji; Morita, Tatsuya; Tatara, Ryohei; Katayama, Hirofumi; Aiki, Sayo; Kitada, Namiki; Fumimoto, Hiromi; Sato, Emi

2015-09-01

Our objective was to explore the effectiveness of a palliative care team (PCT) by investigating potential differences in opioid prescription between patients who had had PCT involvement before admission to an inpatient hospice and those who had not. A total of 221 patients met the criteria; they were divided into an intervention group (n = 140) and a control group (n = 81). The daily dose of opioid before admission to the hospice was significantly higher in the intervention group (P < .001). The difference between the maximum opioid dose and the initial dose, the rate of increase in opioids until death, and the length of stay in the hospice were not significantly different between the groups. A PCT contributes to more appropriate use of opioids before admission to a hospice. © The Author(s) 2014.

Statistical variability and confidence intervals for planar dose QA pass rates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bailey, Daniel W.; Nelms, Benjamin E.; Attwood, Kristopher

Purpose: The most common metric for comparing measured to calculated dose, such as for pretreatment quality assurance of intensity-modulated photon fields, is a pass rate (%) generated using percent difference (%Diff), distance-to-agreement (DTA), or some combination of the two (e.g., gamma evaluation). For many dosimeters, the grid of analyzed points corresponds to an array with a low areal density of point detectors. In these cases, the pass rates for any given comparison criteria are not absolute but exhibit statistical variability that is a function, in part, on the detector sampling geometry. In this work, the authors analyze the statistics ofmore » various methods commonly used to calculate pass rates and propose methods for establishing confidence intervals for pass rates obtained with low-density arrays. Methods: Dose planes were acquired for 25 prostate and 79 head and neck intensity-modulated fields via diode array and electronic portal imaging device (EPID), and matching calculated dose planes were created via a commercial treatment planning system. Pass rates for each dose plane pair (both centered to the beam central axis) were calculated with several common comparison methods: %Diff/DTA composite analysis and gamma evaluation, using absolute dose comparison with both local and global normalization. Specialized software was designed to selectively sample the measured EPID response (very high data density) down to discrete points to simulate low-density measurements. The software was used to realign the simulated detector grid at many simulated positions with respect to the beam central axis, thereby altering the low-density sampled grid. Simulations were repeated with 100 positional iterations using a 1 detector/cm{sup 2} uniform grid, a 2 detector/cm{sup 2} uniform grid, and similar random detector grids. For each simulation, %/DTA composite pass rates were calculated with various %Diff/DTA criteria and for both local and global %Diff normalization techniques. Results: For the prostate and head/neck cases studied, the pass rates obtained with gamma analysis of high density dose planes were 2%-5% higher than respective %/DTA composite analysis on average (ranging as high as 11%), depending on tolerances and normalization. Meanwhile, the pass rates obtained via local normalization were 2%-12% lower than with global maximum normalization on average (ranging as high as 27%), depending on tolerances and calculation method. Repositioning of simulated low-density sampled grids leads to a distribution of possible pass rates for each measured/calculated dose plane pair. These distributions can be predicted using a binomial distribution in order to establish confidence intervals that depend largely on the sampling density and the observed pass rate (i.e., the degree of difference between measured and calculated dose). These results can be extended to apply to 3D arrays of detectors, as well. Conclusions: Dose plane QA analysis can be greatly affected by choice of calculation metric and user-defined parameters, and so all pass rates should be reported with a complete description of calculation method. Pass rates for low-density arrays are subject to statistical uncertainty (vs. the high-density pass rate), but these sampling errors can be modeled using statistical confidence intervals derived from the sampled pass rate and detector density. Thus, pass rates for low-density array measurements should be accompanied by a confidence interval indicating the uncertainty of each pass rate.« less

Amphetamine self-administration in light and moderate drinkers.

PubMed

Stanley, Matthew D; Poole, Mégan M; Stoops, William W; Rush, Craig R

2011-03-01

Light and moderate drinkers respond differently to the effects of abused drugs, including stimulants such as amphetamine. The purpose of this study was to determine whether light and moderate drinkers differ in their sensitivity to the reinforcing and subjective effects of d-amphetamine. We hypothesized that moderate drinkers (i.e., participants that reported consuming at least seven alcohol-containing beverages per week) would be more sensitive to the reinforcing and positive subject-rated effects of d-amphetamine than light drinkers. Data from four studies that employed similar d-amphetamine self-administration procedures and subject-rated drug-effect measures were included in the analysis. Light (n = 17) and moderate (n = 16) drinkers sampled placebo, low (8 to 10 mg), and high (16 to 20 mg) doses of oral d-amphetamine administered in eight capsules. Following sampling sessions, participants worked for a maximum of eight capsules, each containing 12.5% of the previously sampled dose, on a modified progressive-ratio schedule of reinforcement. Both active doses of d-amphetamine functioned as a reinforcer in the moderate drinkers, while only the high dose did so in the light drinkers. The moderate drinkers worked for significantly more capsules that contained the high dose of d-amphetamine than did the light drinkers. d-Amphetamine produced prototypical stimulant-like subjective effects (e.g., dose-dependent increases in ratings of Good Effects; Like Drug and Willing to Take Again). Moderate drinkers reported significantly greater subjective effects than the light drinkers. These results are consistent with those from previous laboratory experiments and suggest that moderate alcohol consumption may increase vulnerability to the abuse-related effects of stimulants. Copyright © 2010 by the Research Society on Alcoholism.

Absorbed dose-to-water protocol applied to synchrotron-generated x-rays at very high dose rates

NASA Astrophysics Data System (ADS)

Fournier, P.; Crosbie, J. C.; Cornelius, I.; Berkvens, P.; Donzelli, M.; Clavel, A. H.; Rosenfeld, A. B.; Petasecca, M.; Lerch, M. L. F.; Bräuer-Krisch, E.

2016-07-01

Microbeam radiation therapy (MRT) is a new radiation treatment modality in the pre-clinical stage of development at the ID17 Biomedical Beamline of the European synchrotron radiation facility (ESRF) in Grenoble, France. MRT exploits the dose volume effect that is made possible through the spatial fractionation of the high dose rate synchrotron-generated x-ray beam into an array of microbeams. As an important step towards the development of a dosimetry protocol for MRT, we have applied the International Atomic Energy Agency’s TRS 398 absorbed dose-to-water protocol to the synchrotron x-ray beam in the case of the broad beam irradiation geometry (i.e. prior to spatial fractionation into microbeams). The very high dose rates observed here mean the ion recombination correction factor, k s , is the most challenging to quantify of all the necessary corrections to apply for ionization chamber based absolute dosimetry. In the course of this study, we have developed a new method, the so called ‘current ramping’ method, to determine k s for the specific irradiation and filtering conditions typically utilized throughout the development of MRT. Using the new approach we deduced an ion recombination correction factor of 1.047 for the maximum ESRF storage ring current (200 mA) under typical beam spectral filtering conditions in MRT. MRT trials are currently underway with veterinary patients at the ESRF that require additional filtering, and we have estimated a correction factor of 1.025 for these filtration conditions for the same ESRF storage ring current. The protocol described herein provides reference dosimetry data for the associated Treatment Planning System utilized in the current veterinary trials and anticipated future human clinical trials.

Quantifying public radiation exposure related to lutetium-177 octreotate therapy for the development of a safe outpatient treatment protocol.

PubMed

Olmstead, Craig; Cruz, Kyle; Stodilka, Robert; Zabel, Pamela; Wolfson, Robert

2015-02-01

Radionuclide therapies, including treatment of neuroendocrine tumors with lutetium-177 (Lu-177) octreotate, often involve hospital admission to minimize radiation exposure to the public. Overnight admission due to Lu-177 octreotate therapy incurs additional cost for the hospital and is an inconvenience for the patient. This study endeavors to characterize the potential radiation risk to caregivers and the public should Lu-177 octreotate therapies be performed on an outpatient basis. Dose rate measurements of radiation emanating from 10 patients were taken 30 min, 4, and 20 h after initiation of Lu-177 octreotate therapy. Instadose radiation dose measurement monitors were also placed around the patients' rooms to assess the potential cumulative radiation exposure during the initial 30 min-4 h after treatment (simulating the hospital-based component of the outpatient model) as well as 4-20 h after treatment (simulating the discharged outpatient portion). The mean recorded dose rate at 30 min, 4, and 20 h after therapy was 20.4, 14.0, and 6.6 μSv/h, respectively. The majority of the cumulative dose readings were below the minimum recordable threshold of 0.03 mSv, with a maximum dose recorded of 0.18 mSv. Given the low dose rate and cumulative levels of radiation measured, the results support that an outpatient Lu-177 octreotate treatment protocol would not jeopardize public safety. Nevertheless, the concept of ALARA still requires that detailed radiation safety protocols be developed for Lu-177 octreotate outpatients to minimize radiation exposure to family members, caregivers, and the general public.

Poster — Thur Eve — 58: Dosimetric validation of electronic compensation for radiotherapy treatment planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gräfe, James; Khan, Rao; Meyer, Tyler

2014-08-15

In this study we investigate the deliverability of dosimetric plans generated by the irregular surface compensator (ISCOMP) algorithm for 6 MV photon beams in Eclipse (Varian Medical System, CA). In contrast to physical tissue compensation, the electronic ISCOMP uses MLCs to dynamically modulate the fluence of a photon beam in order to deliver a uniform dose at a user defined plane in tissue. This method can be used to shield critical organs that are located within the treatment portal or improve dose uniformity by tissue compensation in inhomogeneous regions. Three site specific plans and a set of test fields weremore » evaluated using the γ-metric of 3%/ 3 mm on Varian EPID, MapCHECK, and Gafchromic EBT3 film with a clinical tolerance of >95% passing rates. Point dose measurements with an NRCC calibrated ionization chamber were also performed to verify the absolute dose delivered. In all cases the MapCHECK measured plans met the gamma criteria. The mean passing rate for the six EBT3 film field measurements was 96.2%, with only two fields at 93.4 and 94.0% passing rates. The EPID plans passed for fields encompassing the central ∼10 × 10 cm{sup 2} region of the detector; however for larger fields and greater off-axis distances discrepancies were observed and attributed to the profile corrections and modeling of backscatter in the portal dose calculation. The magnitude of the average percentage difference for 21 ion chamber point dose measurements and 17 different fields was 1.4 ± 0.9%, and the maximum percentage difference was −3.3%. These measurements qualify the algorithm for routine clinical use subject to the same pre-treatment patient specific QA as IMRT.« less

Hypothyroidism as a Consequence of Intensity-Modulated Radiotherapy With Concurrent Taxane-Based Chemotherapy for Locally Advanced Head-and-Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Diaz, Roberto; Jaboin, Jerry J.; Morales-Paliza, Manuel

Purpose: To conduct a retrospective review of 168 consecutively treated locally advanced head-and-neck cancer (LAHNC) patients treated with intensity-modulated radiotherapy (IMRT)/chemotherapy, to determine the rate and risk factors for developing hypothyroidism. Methods and Materials: Intensity-modulated radiotherapy was delivered in 33 daily fractions to 69.3 Gy to gross disease and 56.1 Gy to clinically normal cervical nodes. Dose-volume histograms (DVHs) of IMRT plans were used to determine radiation dose to thyroid and were compared with DVHs using conventional three-dimensional radiotherapy (3D-RT) in 10 of these same patients randomly selected for replanning and with DVHs of 16 patients in whom the thyroidmore » was intentionally avoided during IMRT. Weekly paclitaxel (30 mg/m{sup 2}) and carboplatin area under the curve-1 were given concurrently with IMRT. Results: Sixty-one of 128 evaluable patients (47.7%) developed hypothyroidism after a median of 1.08 years after IMRT (range, 2.4 months to 3.9 years). Age and volume of irradiated thyroid were associated with hypothyroidism development after IMRT. Compared with 3D-RT, IMRT with no thyroid dose constraints resulted in significantly higher minimum, maximum, and median dose (p < 0.0001) and percentage thyroid volume receiving 10, 20, and 60 Gy (p < 0.05). Compared with 3D-RT, IMRT with thyroid dose constraints resulted in lower median dose and percentage thyroid volume receiving 30, 40, and 50 Gy (p < 0.005) but higher minimum and maximum dose (p < 0.005). Conclusions: If not protected, IMRT for LAHNC can result in higher radiation to the thyroid than with conventional 3D-RT. Techniques to reduce dose and volume of radiation to thyroid tissue with IMRT are achievable and recommended.« less

A phase I study of amrubicin and fixed dose of irinotecan (CPT-11) in relapsed small cell lung cancer: Japan multinational trial organization LC0303.

PubMed

Kawahara, Masaaki; Kubo, Akihito; Komuta, Kiyoshi; Fujita, Yuka; Sasaki, Yoshiaki; Fukushima, Masanori; Daimon, Takashi; Furuse, Kiyoyuki; Mishima, Michiaki; Mio, Tadashi

2012-12-01

To determine the maximum tolerated dose of amrubicin (AMR) with a fixed dose of irinotecan (CPT-11). Patients having pathologically proven small cell lung cancer (SCLC) relapsed after one or two chemotherapies, and Eastern Cooperative Oncology Group performance status of 0 to 2 were eligible for the study. CPT-11 was delivered as 50 mg/m2 on days 1 and 8, every 21 days. AMR was delivered on day 1. Doses of AMR were level 1: 80 mg/m2, level 2: 90 mg/m2, and level 3: 100 mg/m2. Dose elevation was determined using the modified continuous reassessment method. Tolerability was assessed after the first cycle. Another two cycles were conducted when disease progression or unacceptable toxicities were not observed. Eighteen patients (mean age: 66.3 years) were enrolled. A total of 40 courses were conducted. Grade 3/4 toxicities of the first cycle were leukocytopenia: 11 (61%, grade 3/4: 8/3); neutropenia: 15 (83%, grade 3/4: 6/9); and thrombocytopenia: three (17%, grade 3/4: 2/1). Other grade 3 toxicities observed were febrile neutropenia, one; infection, three; diarrhea, one; and dyspnea, one. Dose-limiting toxicity was observed in two of six patients at level 2 (neutropenia and febrile neutropenia) and in one of six at level 3 (thrombocytopenia and infection). The maximum tolerated dose was level 3, and so, the recommended dose for phase II trials was judged to be 90 mg/m2. Objective response was obtained in four of eight patients who were able to evaluate responses. Median survival time was 13 months, with 68% at 1-year survival rate. This combination was well tolerated and showed encouraging activities in SCLC. Randomized phase II trials are being planned in chemonaive SCLC.

Long-term outcome of accelerated partial breast irradiation using a multilumen balloon applicator in a patient with existing breast implants.

PubMed

Akhtari, Mani; Nitsch, Paige L; Bass, Barbara L; Teh, Bin S

2015-01-01

Accelerated partial breast irradiation is now an accepted component of breast-conserving therapy. However, data regarding long-term outcomes of patients treated with multilumen catheter systems who have existing breast implants are limited. We report the treatment and outcome of our patient who had existing bilateral silicone subpectoral implants at the time of presentation. Ultrasound-guided core needle biopsy of the right breast showed infiltrating mucinous carcinoma. Right breast lumpectomy revealed an 8 mm area of infiltrating ductal carcinoma with mucinous features and nuclear grade 1. A 4-5 cm Contura (Bard Biopsy Systems, Tempe, AZ) device was placed, and she was treated over the course of 5 days twice daily to a dose of 34 Gy using a high-dose-rate iridium-192 source. The planning target volume for evaluation was 73.9 cc. The percentage of the planning target volume for evaluation receiving 90%, 95%, and 100% of the prescribed dose was 99.9%, 99.3%, and 97.8%, respectively. The total implant volume was 234.5 cc and received a mean dose of 15.4 Gy and a maximum dose of 72.8 Gy. The percentage of implant volume receiving 50%, 75%, 100%, and 200% of the prescribed dose was 31.1%, 16.5%, 8.6%, 2.0%, and 0%, respectively. Maximum skin dose was 97% of the prescribed dose. With a followup of nearly 5 years, she continues to be cancer free with minimal late toxicities and good to excellent cosmetic outcome. Accelerated partial breast irradiation using a multilumen balloon applicator in patients with existing breast implants can safely be performed with excellent long-term cosmetic outcome. Further studies are needed to establish the absolute dosimetric tolerance of breast implants. Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Dosimetric evaluation of high-dose-rate interstitial brachytherapy boost treatments for localized prostate cancer.

PubMed

Fröhlich, Georgina; Agoston, Péter; Lövey, József; Somogyi, András; Fodor, János; Polgár, Csaba; Major, Tibor

2010-07-01

To quantitatively evaluate the dose distributions of high-dose-rate (HDR) prostate implants regarding target coverage, dose homogeneity, and dose to organs at risk. Treatment plans of 174 implants were evaluated using cumulative dose-volume histograms (DVHs). The planning was based on transrectal ultrasound (US) imaging, and the prescribed dose (100%) was 10 Gy. The tolerance doses to rectum and urethra were 80% and 120%, respectively. Dose-volume parameters for target (V90, V100, V150, V200, D90, D(min)) and quality indices (DNR [dose nonuniformity ratio], DHI [dose homogeneity index], CI [coverage index], COIN [conformal index]) were calculated. Maximum dose in reference points of rectum (D(r)) and urethra (D(u)), dose to volume of 2 cm(3) of the rectum (D(2ccm)), and 0.1 cm(3) and 1% of the urethra (D(0.1ccm) and D1) were determined. Nonparametric correlation analysis was performed between these parameters. The median number of needles was 16, the mean prostate volume (V(p)) was 27.1 cm(3). The mean V90, V100, V150, and V200 were 99%, 97%, 39%, and 13%, respectively. The mean D90 was 109%, and the D(min) was 87%. The mean doses in rectum and urethra reference points were 75% and 119%, respectively. The mean volumetric doses were D(2ccm) = 49% for the rectum, D(0.1ccm) = 126%, and D1 = 140% for the urethra. The mean DNR was 0.37, while the DHI was 0.60. The mean COIN was 0.66. The Spearman rank order correlation coefficients for volume doses to rectum and urethra were R(D(r),D(2ccm)) = 0.69, R(D(u),D0.(1ccm)) = 0.64, R(D(u),D1) = 0.23. US-based treatment plans for HDR prostate implants based on the real positions of catheters provided acceptable dose distributions. In the majority of the cases, the doses to urethra and rectum were kept below the defined tolerance levels. For rectum, the dose in reference points correlated well with dose-volume parameters. For urethra dose characterization, the use of D1 volumetric parameter is recommended.

Effect of the Maximum Dose on White Matter Fiber Bundles Using Longitudinal Diffusion Tensor Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Tong; Chapman, Christopher H.; Tsien, Christina

2016-11-01

Purpose: Previous efforts to decrease neurocognitive effects of radiation focused on sparing isolated cortical structures. We hypothesize that understanding temporal, spatial, and dosimetric patterns of radiation damage to whole-brain white matter (WM) after partial-brain irradiation might also be important. Therefore, we carried out a study to develop the methodology to assess radiation therapy (RT)–induced damage to whole-brain WM bundles. Methods and Materials: An atlas-based, automated WM tractography analysis was implemented to quantify longitudinal changes in indices of diffusion tensor imaging (DTI) of 22 major WM fibers in 33 patients with predominantly low-grade or benign brain tumors treated by RT. Sixmore » DTI scans per patient were performed from before RT to 18 months after RT. The DTI indices and planned doses (maximum and mean doses) were mapped onto profiles of each of 22 WM bundles. A multivariate linear regression was performed to determine the main dose effect as well as the influence of other clinical factors on longitudinal percentage changes in axial diffusivity (AD) and radial diffusivity (RD) from before RT. Results: Among 22 fiber bundles, AD or RD changes in 12 bundles were affected significantly by doses (P<.05), as the effect was progressive over time. In 9 elongated tracts, decreased AD or RD was significantly related to maximum doses received, consistent with a serial structure. In individual bundles, AD changes were up to 11.5% at the maximum dose locations 18 months after RT. The dose effect on WM was greater in older female patients than younger male patients. Conclusions: Our study demonstrates for the first time that the maximum dose to the elongated WM bundles causes post-RT damage in WM. Validation and correlative studies are necessary to determine the ability and impact of sparing these bundles on preserving neurocognitive function after RT.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Small, Katherine; Kelly, Chris; Beldham-Collins, Rachael

A comparative study was conducted comparing the difference between (1) conformal radiotherapy (CRT) to the whole breast with sequential boost excision cavity plans and (2) intensity-modulated radiation therapy (IMRT) to the whole breast with simultaneously integrated boost to the excision cavity. The computed tomography (CT) data sets of 25 breast cancer patients were used and the results analysed to determine if either planning method produced superior plans. CT data sets from 25 past breast cancer patients were planned using (1) CRT prescribed to 50 Gy in 25 fractions (Fx) to the whole-breast planning target volume (PTV) and 10 Gy inmore » 5Fx to the excision cavity and (2) IMRT prescribed to 60 Gy in 25Fx, with 60 Gy delivered to the excision cavity PTV and 50 Gy delivered to the whole-breast PTV, treated simultaneously. In total, 50 plans were created, with each plan evaluated by PTV coverage using conformity indices, plan maximum dose, lung dose, and heart maximum dose for patients with left-side lesions. CRT plans delivered the lowest plan maximum doses in 56% of cases (average CRT = 6314.34 cGy, IMRT = 6371.52 cGy). They also delivered the lowest mean lung dose in 68% of cases (average CRT = 1206.64 cGy, IMRT = 1288.37 cGy) and V20 in 88% of cases (average CRT = 20.03%, IMRT = 21.73%) and V30 doses in 92% of cases (average CRT = 16.82%, IMRT = 17.97%). IMRT created more conformal plans, using both conformity index and conformation number, in every instance, and lower heart maximum doses in 78.6% of cases (average CRT = 5295.26 cGy, IMRT = 5209.87 cGy). IMRT plans produced superior dose conformity and shorter treatment duration, but a slightly higher planning maximum and increased lung doses. IMRT plans are also faster to treat on a daily basis, with shorter fractionation.« less

Pharmacokinetics, Pharmacodynamics and Population Pharmacokinetic/Pharmacodynamic Modelling of Bilastine, a Second-Generation Antihistamine, in Healthy Japanese Subjects.

PubMed

Togawa, Michinori; Yamaya, Hidetoshi; Rodríguez, Mónica; Nagashima, Hirotaka

2016-12-01

Bilastine is a novel second-generation antihistamine for the symptomatic treatment of allergic rhinitis and urticaria. The objective of this study was to evaluate the pharmacokinetics, pharmacodynamics, and tolerability of bilastine following single and multiple oral doses in healthy Japanese subjects. The pharmacokinetic and pharmacodynamic profiles were compared with those reported in Caucasian subjects. In a single-blind, randomized, placebo-controlled, parallel-group, single- and multiple-ascending dose study, bilastine tablets were administered at single doses of 10, 20, and 50 mg (Part I), and once daily for 14 days at 20 and 50 mg (Part II). After single oral doses, maximum plasma concentrations (C max ) were reached at 1.0-1.5 h postdose. Plasma exposure [C max and area under the plasma concentration-time curve (AUC)] increased dose-proportionally at single doses of 10-50 mg. In repeated-dose administration, no remarkable differences were observed between Day 1 and Day 14 for C max or AUC. For inhibitory effects on wheal and flare response, bilastine 20 and 50 mg showed significant inhibition from 1.5 h after administration as compared with placebo, and the significant effect persisted for 24 h after administration. The rates of adverse events (AEs) were comparable between bilastine and placebo in both Part I and Part II. In addition, no dose- or administration period-dependent tendency of increase in rate of AEs or worsening of severity was observed. Bilastine exhibits similar single- and multiple-dose pharmacokinetic and pharmacodynamic characteristics in healthy Japanese subjects compared with those observed in Caucasian subjects in previous studies.

A quality assurance device for measuring afterloader performance and transit dose for nasobiliary high-dose-rate brachytherapy.

PubMed

Deufel, Christopher L; Mullins, John P; Zakhary, Mark J

2018-05-17

Nasobiliary high-dose-rate (HDR) brachytherapy has emerged as an effective tool to boost the radiation dose for patients with unresectable perihilar cholangiocarcinoma. This work describes a quality assurance (QA) tool for measuring the HDR afterloader's performance, including the transit dose, when the source wire travels through a tortuous nasobiliary catheter path. The nasobiliary QA device was designed to mimic the anatomical path of a nasobiliary catheter, including the nasal, stomach, duodenum, and bile duct loops. Two of these loops, the duodenum and bile duct loops, have adjustable radii of curvature, resulting in the ability to maximize stress on the source wire in transit. The device was used to measure the performance over time for the HDR afterloader and the differences between intraluminal catheter lots. An upper limit on the transit dose was also measured using radiochromic film and compared with a simple theoretical model. The QA device was capable of detecting performance variations among nasobiliary catheter lots and following radioactive source replacement. The transit dose from a nasobiliary treatment increased by up to one order of magnitude when the source wire encountered higher than normal friction. Three distinct travel speeds of the source wire were observed: 5.2, 17.4, and 54.7 cm/s. The maximum transit dose was 0.3 Gy at a radial distance of 5 mm from a 40.3 kU 192 Ir source. The source wire encounters substantially greater friction when it navigates through the nasobiliary brachytherapy catheter. A QA tool that mimics the nasal, stomach, duodenum, and bile duct loops may be used to evaluate transit dose and the afterloader's performance over time. Copyright © 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Comparison of organ doses for patients undergoing balloon brachytherapy of the breast with HDR 192Ir or electronic sources using Monte Carlo simulations in a heterogeneous human phantom1

PubMed Central

Mille, Matthew M.; Xu, X. George; Rivard, Mark J.

2010-01-01

Purpose: Accelerated partial breast irradiation via interstitial balloon brachytherapy is a fast and effective treatment method for certain early stage breast cancers. The radiation can be delivered using a conventional high-dose rate (HDR) 192Ir gamma-emitting source or a novel electronic brachytherapy (eBx) source which uses lower energy x rays that do not penetrate as far within the patient. A previous study [A. Dickler, M. C. Kirk, N. Seif, K. Griem, K. Dowlatshahi, D. Francescatti, and R. A. Abrams, “A dosimetric comparison of MammoSite high-dose-rate brachytherapy and Xoft Axxent electronic brachytherapy,” Brachytherapy 6, 164–168 (2007)] showed that the target dose is similar for HDR 192Ir and eBx. This study compares these sources based on the dose received by healthy organs and tissues away from the treatment site. Methods: A virtual patient with left breast cancer was represented by a whole-body, tissue-heterogeneous female voxel phantom. Monte Carlo methods were used to calculate the dose to healthy organs in a virtual patient undergoing balloon brachytherapy of the left breast with HDR 192Ir or eBx sources. The dose-volume histograms for a few organs which received large doses were also calculated. Additional simulations were performed with all tissues in the phantom defined as water to study the effect of tissue inhomogeneities. Results: For both HDR 192Ir and eBx, the largest mean organ doses were received by the ribs, thymus gland, left lung, heart, and sternum which were close to the brachytherapy source in the left breast. eBx yielded mean healthy organ doses that were more than a factor of ∼1.4 smaller than for HDR 192Ir for all organs considered, except for the three closest ribs. Excluding these ribs, the average and median dose-reduction factors were ∼28 and ∼11, respectively. The volume distribution of doses in nearby soft tissue organs that were outside the PTV were also improved with eBx. However, the maximum dose to the closest rib with the eBx source was 5.4 times greater than that of the HDR 192Ir source. The ratio of tissue-to-water maximum rib dose for the eBx source was ∼5. Conclusions: The results of this study indicate that eBx may offer lower toxicity to most healthy tissues, except nearby bone. TG-43 methods have a tendency to underestimate dose to bone, especially the ribs. Clinical studies evaluating the negative health effects caused by irradiating healthy organs are needed so that physicians can better understand when HDR 192Ir or eBx might best benefit a patient. PMID:20229875

[The use of polymer gel dosimetry to measure dose distribution around metallic implants].

PubMed

Nagahata, Tomomasa; Yamaguchi, Hajime; Monzen, Hajime; Nishimura, Yasumasa

2014-10-01

A semi-solid polymer dosimetry system using agar was developed to measure the dose distribution close to metallic implants. Dosimetry of heterogeneous fields where electron density markedly varies is often problematic. This prompted us to develop a polymer gel dosimetry technique using agar to measure the dose distribution near substance boundaries. Varying the concentration of an oxygen scavenger (tetra-hydroxymethyl phosphonium chloride) showed the absorbed dose and transverse relaxation rate of the magnetic resonance signal to be linear between 3 and 12 Gy. Although a change in the dosimeter due to oxidization was observed in room air after 24 hours, no such effects were observed in the first 4 hours. The dose distribution around the metal implants was measured using agar dosimetry. The metals tested were a lead rod, a titanium hip joint, and a metallic stent. A maximum 30% dose increase was observed near the lead rod, but only a 3% increase in the absorbed dose was noted near the surface of the titanium hip joint and metallic stent. Semi-solid polymer dosimetry using agar thus appears to be a useful method for dosimetry around metallic substances.

Melphalan, prednisone, thalidomide and defibrotide in relapsed/refractory multiple myeloma: results of a multicenter phase I/II trial.

PubMed

Palumbo, Antonio; Larocca, Alessandra; Genuardi, Mariella; Kotwica, Katarzyna; Gay, Francesca; Rossi, Davide; Benevolo, Giulia; Magarotto, Valeria; Cavallo, Federica; Bringhen, Sara; Rus, Cecilia; Masini, Luciano; Iacobelli, Massimo; Gaidano, Gianluca; Mitsiades, Constantine; Anderson, Kenneth; Boccadoro, Mario; Richardson, Paul

2010-07-01

Defibrotide is a novel orally bioavailable polydisperse oligonucleotide with anti-thrombotic and anti-adhesive effects. In SCID/NOD mice, defibrotide showed activity in human myeloma xenografts. This phase I/II study was conducted to identify the most appropriate dose of defibrotide in combination with melphalan, prednisone and thalidomide in patients with relapsed and relapsed/refractory multiple myeloma, and to determine its safety and tolerability as part of this regimen. This was a phase I/II, multicenter, dose-escalating, non-comparative, open label study. Oral melphalan was administered at a dose of 0.25 mg/kg on days 1-4, prednisone at a dose of 1.5 mg/kg also on days 1-4 and thalidomide at a dose of 50-100 mg/day continuously. Defibrotide was administered orally at three dose-levels: 2.4, 4.8 or 7.2 g on days 1-4 and 1.6, 3.2, or 4.8 g on days 5-35. Twenty-four patients with relapsed/refractory multiple myeloma were enrolled. No dose-limiting toxicity was observed. In all patients, the complete response plus very good partial response rate was 9%, and the partial response rate was 43%. The 1-year progression-free survival and 1-year overall survival rates were 34% and 90%, respectively. The most frequent grade 3-4 adverse events included neutropenia, thrombocytopenia, anemia and fatigue. Deep vein thrombosis was reported in only one patient. This combination of melphalan, prednisone and thalidomide together with defibrotide showed anti-tumor activity with a favorable tolerability. The maximum tolerated dose of defibrotide was identified as 7.2 g p.o. on days 1-4 followed by 4.8 g p.o. on days 5-35. Further trials are needed to confirm the role of this regimen and to evaluate the combination of defibrotide with new drugs.

Melphalan, prednisone, thalidomide and defibrotide in relapsed/refractory multiple myeloma: results of a multicenter phase I/II trial

PubMed Central

Palumbo, Antonio; Larocca, Alessandra; Genuardi, Mariella; Kotwica, Katarzyna; Gay, Francesca; Rossi, Davide; Benevolo, Giulia; Magarotto, Valeria; Cavallo, Federica; Bringhen, Sara; Rus, Cecilia; Masini, Luciano; Iacobelli, Massimo; Gaidano, Gianluca; Mitsiades, Constantine; Anderson, Kenneth; Boccadoro, Mario; Richardson, Paul

2010-01-01

Background Defibrotide is a novel orally bioavailable polydisperse oligonucleotide with anti-thrombotic and anti-adhesive effects. In SCID/NOD mice, defibrotide showed activity in human myeloma xenografts. This phase I/II study was conducted to identify the most appropriate dose of defibrotide in combination with melphalan, prednisone and thalidomide in patients with relapsed and relapsed/refractory multiple myeloma, and to determine its safety and tolerability as part of this regimen. Design and Methods This was a phase I/II, multicenter, dose-escalating, non-comparative, open label study. Oral melphalan was administered at a dose of 0.25 mg/kg on days 1–4, prednisone at a dose of 1.5 mg/kg also on days 1–4 and thalidomide at a dose of 50–100 mg/day continuously. Defibrotide was administered orally at three dose-levels: 2.4, 4.8 or 7.2 g on days 1–4 and 1.6, 3.2, or 4.8 g on days 5–35. Results Twenty-four patients with relapsed/refractory multiple myeloma were enrolled. No dose-limiting toxicity was observed. In all patients, the complete response plus very good partial response rate was 9%, and the partial response rate was 43%. The 1-year progression-free survival and 1-year overall survival rates were 34% and 90%, respectively. The most frequent grade 3–4 adverse events included neutropenia, thrombocytopenia, anemia and fatigue. Deep vein thrombosis was reported in only one patient. Conclusions This combination of melphalan, prednisone and thalidomide together with defibrotide showed anti-tumor activity with a favorable tolerability. The maximum tolerated dose of defibrotide was identified as 7.2 g p.o. on days 1–4 followed by 4.8 g p.o. on days 5–35. Further trials are needed to confirm the role of this regimen and to evaluate the combination of defibrotide with new drugs (ClinicalTrials.gov Identifier: NCT00406978). PMID:20053869

The use of paracetamol (acetaminophen) among a community sample of people with chronic non-cancer pain prescribed opioids.

PubMed

Hoban, B; Larance, B; Gisev, N; Nielsen, S; Cohen, M; Bruno, R; Shand, F; Lintzeris, N; Hall, W; Farrell, M; Degenhardt, L

2015-11-01

The regular use of simple analgesics in addition to opioids such as paracetamol (or acetaminophen) is recommended for persistent pain to enhance analgesia. Few studies have examined the frequency and doses of paracetamol among people with chronic non-cancer pain including use above the recommended maximum daily dose. To assess (i) the prevalence of paracetamol use among people with chronic non-cancer pain prescribed opioids, (ii) assess the prevalence of paracetamol use above the recommended maximum daily dose and (iii) assess correlates of people who used paracetamol above the recommended maximum daily dose including: age, gender, income, education, pain severity and interference, use of paracetamol/opioid combination analgesics, total opioid dose, depression, anxiety, pain self-efficacy or comorbid substance use, among people prescribed opioids for chronic non-cancer pain. This study draws on baseline data collected for the Pain and Opioids IN Treatment (POINT) study and utilises data from 962 interviews and medication diaries. The POINT study is national prospective cohort of people with chronic non-cancer pain prescribed opioids. Participants were recruited from randomly selected pharmacies across Australia. Sixty-three per cent of the participants had used paracetamol in the past week (95% CI = 59.7-65.8). Among the paracetamol users 22% (95% CI = 19.3-24.6) had used paracetamol/opioid combination analgesics and 4.8% (95% CI = 3.6-6.3) had used paracetamol above the recommended maximum daily dose (i.e. > 4000 mg/day). Following binomial logistic regression (χ(2) = 25.98, df = 10, p = 0.004), people who had taken above the recommended maximum daily dose were less likely to have low income (AOR = 0.52, 95% CI = 0.27-0.99), more likely to use paracetamol/opioid combination analgesics (AOR = 2.01, 95% CI = 1.02-3.98) and more likely to take a higher opioid dose (AOR = 1.00, 95% CI = 1.00-1.01). The majority of people with chronic non-cancer pain prescribed opioids report using paracetamol appropriately. High income, use of paracetamol/opioid combination analgesics and higher opioid dose were independently associated with paracetamol use above the recommended maximum daily dose. © 2015 John Wiley & Sons Ltd.

Contura Multi-Lumen Balloon breast brachytherapy catheter: comparative dosimetric findings of a phase 4 trial.

PubMed

Arthur, Douglas W; Vicini, Frank A; Todor, Dorin A; Julian, Thomas B; Cuttino, Laurie W; Mukhopadhyay, Nitai D

2013-06-01

Final dosimetric findings of a completed, multi-institutional phase 4 registry trial using the Contura Multi-Lumen Balloon (MLB) breast brachytherapy catheter to deliver accelerated partial breast irradiation (APBI) in patients with early-stage breast cancer are presented. Three dosimetric plans with identical target coverage were generated for each patient for comparison: multilumen multidwell (MLMD); central-lumen multidwell (CLMD); and central-lumen single-dwell (CLSD) loading of the Contura catheter. For this study, a successful treatment plan achieved ideal dosimetric goals and included the following: ≥ 95% of the prescribed dose (PD) covering ≥ 95% of the target volume (TV); maximum skin dose ≤ 125% of the PD; maximum rib dose ≤ 145% of the PD; and V150 ≤50 cc and V200 ≤ 10 cc. Between January 2008 and February 2011, 23 institutions participated. A total of 318 patients were available for dosimetric review. Using the Contura MLB, all dosimetric criteria were met in 78.93% of cases planned with MLMD versus 55.38% with the CLMD versus 37.66% with the CLSD (P ≤.0001). Evaluating all patients with the full range of skin to balloon distance represented, median maximum skin dose was reduced by 12% and median maximum rib dose by 13.9% when using MLMD-based dosimetric plans compared to CLSD. The dosimetric benefit of MLMD was further demonstrated in the subgroup of patients where skin thickness was <5 mm, where MLMD use allowed a 38% reduction in median maximum skin dose over CLSD. For patients with rib distance <5 mm, the median maximum rib dose reduction was 27%. Use of the Contura MLB catheter produced statistically significant improvements in dosimetric capabilities between CLSD and CLMD treatments. This device approach demonstrates the ability not only to overcome the barriers of limited skin thickness and close rib proximity, but to consistently achieve a higher standard of dosimetric planning goals. Copyright © 2013 Elsevier Inc. All rights reserved.

Contura Multi-Lumen Balloon Breast Brachytherapy Catheter: Comparative Dosimetric Findings of a Phase 4 Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arthur, Douglas W., E-mail: darthur@mcvh-vcu.edu; Vicini, Frank A.; Todor, Dorin A.

2013-06-01

Purpose: Final dosimetric findings of a completed, multi-institutional phase 4 registry trial using the Contura Multi-Lumen Balloon (MLB) breast brachytherapy catheter to deliver accelerated partial breast irradiation (APBI) in patients with early-stage breast cancer are presented. Methods and Materials: Three dosimetric plans with identical target coverage were generated for each patient for comparison: multilumen multidwell (MLMD); central-lumen multidwell (CLMD); and central-lumen single-dwell (CLSD) loading of the Contura catheter. For this study, a successful treatment plan achieved ideal dosimetric goals and included the following: ≥95% of the prescribed dose (PD) covering ≥95% of the target volume (TV); maximum skin dose ≤125%more » of the PD; maximum rib dose ≤145% of the PD; and V150 ≤50 cc and V200 ≤10 cc. Results: Between January 2008 and February 2011, 23 institutions participated. A total of 318 patients were available for dosimetric review. Using the Contura MLB, all dosimetric criteria were met in 78.93% of cases planned with MLMD versus 55.38% with the CLMD versus 37.66% with the CLSD (P≤.0001). Evaluating all patients with the full range of skin to balloon distance represented, median maximum skin dose was reduced by 12% and median maximum rib dose by 13.9% when using MLMD-based dosimetric plans compared to CLSD. The dosimetric benefit of MLMD was further demonstrated in the subgroup of patients where skin thickness was <5 mm, where MLMD use allowed a 38% reduction in median maximum skin dose over CLSD. For patients with rib distance <5 mm, the median maximum rib dose reduction was 27%. Conclusions: Use of the Contura MLB catheter produced statistically significant improvements in dosimetric capabilities between CLSD and CLMD treatments. This device approach demonstrates the ability not only to overcome the barriers of limited skin thickness and close rib proximity, but to consistently achieve a higher standard of dosimetric planning goals.« less

SU-E-T-598: Clinical Experience of Configuration, Commission and Implementation for SmartArc with MOSAIQ R&V System.

PubMed

Kong, X; Clausen, C; Wang, S

2012-06-01

Clinical experience for configuration, commission and implementation of SmartArc with MOSAIQ R&V system. SmartArc is Pinnacle's solution for VMAT. On July 2011 we updated to Pinnacle 9.0 and purchased SmartArc. A standalone Eclipse workstation has been used 3 years for VMAT planning. Our clinical setting: Mosaiq 2.2; Varian Trilogy driven by 4DiTC and Varian 21ex driven by sequencer. Some key physics parameters have been studied: machine dose rate; MLC leaf speed; Leaf motion per gantry rotation. Tabletop was created by user to improve the dose accuracy for planning. In-house sandwich phantom was used with MapCheck for planner dose verification. A PTW 0.6cc ion chamber was included for absolute dose comparison. A copy of current machine data with default highest dose rate is recommended. It is due to after 10th iteration of optimization, the default dose rate will kick in. 2.5cm/s is the constraint for Varian Millennium 120 MLC; a buffer zone of 10% is suggested to reduce the MLC error on treatment. 2.25cm/s is used in our configuration. This results in MLC interlock if not configured correct. Maximum leaf motion per gantry rotation of 0.46cm/degree has to be checked for planning with Mosaiq R&V. Otherwise, undeliverable plan will show up sometimes on 4DiTC.Tabletop was exported as a DICOM structure from Eclipse to Pinnacle; we created a ROI template based on the matched tabletop.QA using in-house phantom for different sites were tested. Results for both planner dose and absolute chamber measurement are satisfactory. Special attentions need to be paid for dose rate, MLC leaf speed, leaf motion per gantry rotation when configuring SmartArc. Varian 21ex is supported but is slow for clinical delivery. Users need to create your own tabletop to improve planning accuracy. Conventional commission procedures for RapidArc also apply for SmartArc. © 2012 American Association of Physicists in Medicine.

A phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13 in patients with relapsed or refractory Hodgkin lymphoma.

PubMed

Rothe, Achim; Sasse, Stephanie; Topp, Max S; Eichenauer, Dennis A; Hummel, Horst; Reiners, Katrin S; Dietlein, Markus; Kuhnert, Georg; Kessler, Joerg; Buerkle, Carolin; Ravic, Miroslav; Knackmuss, Stefan; Marschner, Jens-Peter; Pogge von Strandmann, Elke; Borchmann, Peter; Engert, Andreas

2015-06-25

AFM13 is a bispecific, tetravalent chimeric antibody construct (TandAb) designed for the treatment of CD30-expressing malignancies. AFM13 recruits natural killer (NK) cells via binding to CD16A as immune effector cells. In this phase 1 dose-escalation study, 28 patients with heavily pretreated relapsed or refractory Hodgkin lymphoma received AFM13 at doses of 0.01 to 7 mg/kg body weight. Primary objectives were safety and tolerability. Secondary objectives included pharmacokinetics, antitumor activity, and pharmacodynamics. Adverse events were generally mild to moderate. The maximum tolerated dose was not reached. Pharmacokinetics assessment revealed a half-life of up to 19 hours. Three of 26 evaluable patients achieved partial remission (11.5%) and 13 patients achieved stable disease (50%), with an overall disease control rate of 61.5%. AFM13 was also active in brentuximab vedotin-refractory patients. In 13 patients who received doses of ≥1.5 mg/kg AFM13, the overall response rate was 23% and the disease control rate was 77%. AFM13 treatment resulted in a significant NK-cell activation and a decrease of soluble CD30 in peripheral blood. In conclusion, AFM13 represents a well-tolerated, safe, and active targeted immunotherapy of Hodgkin lymphoma. A phase 2 study is currently planned to optimize the dosing schedule in order to further improve the therapeutic efficacy. This phase 1 study was registered at www.clinicaltrials.gov as #NCT01221571. © 2015 by The American Society of Hematology.

A phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13 in patients with relapsed or refractory Hodgkin lymphoma

PubMed Central

Rothe, Achim; Sasse, Stephanie; Topp, Max S.; Eichenauer, Dennis A.; Hummel, Horst; Reiners, Katrin S.; Dietlein, Markus; Kuhnert, Georg; Kessler, Joerg; Buerkle, Carolin; Ravic, Miroslav; Knackmuss, Stefan; Marschner, Jens-Peter; Pogge von Strandmann, Elke; Borchmann, Peter

2015-01-01

AFM13 is a bispecific, tetravalent chimeric antibody construct (TandAb) designed for the treatment of CD30-expressing malignancies. AFM13 recruits natural killer (NK) cells via binding to CD16A as immune effector cells. In this phase 1 dose-escalation study, 28 patients with heavily pretreated relapsed or refractory Hodgkin lymphoma received AFM13 at doses of 0.01 to 7 mg/kg body weight. Primary objectives were safety and tolerability. Secondary objectives included pharmacokinetics, antitumor activity, and pharmacodynamics. Adverse events were generally mild to moderate. The maximum tolerated dose was not reached. Pharmacokinetics assessment revealed a half-life of up to 19 hours. Three of 26 evaluable patients achieved partial remission (11.5%) and 13 patients achieved stable disease (50%), with an overall disease control rate of 61.5%. AFM13 was also active in brentuximab vedotin–refractory patients. In 13 patients who received doses of ≥1.5 mg/kg AFM13, the overall response rate was 23% and the disease control rate was 77%. AFM13 treatment resulted in a significant NK-cell activation and a decrease of soluble CD30 in peripheral blood. In conclusion, AFM13 represents a well-tolerated, safe, and active targeted immunotherapy of Hodgkin lymphoma. A phase 2 study is currently planned to optimize the dosing schedule in order to further improve the therapeutic efficacy. This phase 1 study was registered at www.clinicaltrials.gov as #NCT01221571. PMID:25887777

Potential for reduced radiation‐induced toxicity using intensity‐modulated arc therapy for whole‐brain radiotherapy with hippocampal sparing

PubMed Central

Sood, Sumit; Lominska, Christopher; Kumar, Parvesh; Badkul, Rajeev; Jiang, Hongyu; Wang, Fen

2015-01-01

The purpose of this study was to retrospectively investigate the accuracy, plan quality, and efficiency of using intensity‐modulated arc therapy (IMAT) for whole brain radiotherapy (WBRT) patients with sparing not only the hippocampus (following RTOG 0933 compliance criteria) but also other organs at risk (OARs). A total of 10 patients previously treated with nonconformal opposed laterals whole‐brain radiotherapy (NC‐WBRT) were retrospectively replanned for hippocampal sparing using IMAT treatment planning. The hippocampus was volumetrically contoured on fused diagnostic T1‐weighted MRI with planning CT images and hippocampus avoidance zone (HAZ) was generated using a 5 mm uniform margin around the hippocampus. Both hippocampi were defined as one paired organ. Whole brain tissue minus HAZ was defined as the whole‐brain planning target volume (WB‐PTV). Highly conformal IMAT plans were generated in the Eclipse treatment planning system for Novalis TX linear accelerator consisting of high‐definition multileaf collimators (HD‐MLCs: 2.5 mm leaf width at isocenter) and 6 MV beam for a prescription dose of 30 Gy in 10 fractions following RTOG 0933 dosimetric criteria. Two full coplanar arcs with orbits avoidance sectors were used. In addition to RTOG criteria, doses to other organs at risk (OARs), such as parotid glands, cochlea, external/middle ear canals, skin, scalp, optic pathways, brainstem, and eyes/lens, were also evaluated. Subsequently, dose delivery efficiency and accuracy of each IMAT plan was assessed by delivering quality assurance (QA) plans with a MapCHECK device, recording actual beam‐on time and measuring planed vs. measured dose agreement using a gamma index. On IMAT plans, following RTOG 0933 dosimetric criteria, the maximum dose to WB‐PTV, mean WB‐PTV D2%, and mean WB‐PTV D98% were 34.9±0.3 Gy,33.2±0.4 Gy, and 26.0±0.4 Gy, respectively. Accordingly, WB‐PTV received the prescription dose of 30 Gy and mean V30 was 90.5%±0.5%. The D100%, and mean and maximum doses to hippocampus were 8.4±0.3 Gy,11.2±0.3 Gy, and 15.6±0.4 Gy, on average, respectively. The mean values of homogeneity index (HI) and conformity index (CI) were 0.23×0.02 and 0.96×0.02, respectively. The maximum point dose to WB‐PTV was 35.3 Gy, well below the optic pathway tolerance of 37.5 Gy. In addition, compared to NC‐WBRT, dose reduction of mean and maximum of parotid glands from IMAT were 65% and 50%, respectively. Ear canals mean and maximum doses were reduced by 26% and 12%, and mean and maximum scalp doses were reduced by 9 Gy (32%) and 2 Gy (6%), on average, respectively. The mean dose to skin was 9.7 Gy with IMAT plans compared to 16 Gy with conventional NC‐WBRT, demonstrating that absolute reduction of skin dose by a factor of 2. The mean values of the total number of monitor units (MUs) and actual beam on time were 719×44 and 2.34×0.14 min, respectively. The accuracy of IMAT QA plan delivery was (98.1±0.8) %, on average, with a 3%/3 mm gamma index passing rate criteria. All of these plans were considered clinically acceptable per RTOG 0933 criteria. IMAT planning provided highly conformal and homogenous plan with a fast and effective treatment option for WBRT patients, sparing not only hippocampi but also other OARs, which could potentially result in an additional improvement of the quality life (QoL). In the future, we plan to evaluate the clinical potential of IMAT planning and treatment option with hippocampal and other OARs avoidance in our patient's cohort and asses the QoL of the WBRT patients, as well as simultaneous integrated boost (SIB) for the brain metastases diseases. PACS number: 87 PMID:26699321

The effect of dose heterogeneity on radiation risk in medical imaging.

PubMed

Samei, Ehsan; Li, Xiang; Chen, Baiyu; Reiman, Robert

2013-06-01

The current estimations of risk associated with medical imaging procedures rely on assessing the organ dose via direct measurements or simulation. The dose to each organ is assumed to be homogeneous. To take into account the differences in radiation sensitivities, the mean organ doses are weighted by a corresponding tissue-weighting coefficients provided by ICRP to calculate the effective dose, which has been used as a surrogate of radiation risk. However, those coefficients were derived under the assumption of a homogeneous dose distribution within each organ. That assumption is significantly violated in most medical-imaging procedures. In helical chest CT, for example, superficial organs (e.g. breasts) demonstrate a heterogeneous dose distribution, whereas organs on the peripheries of the irradiation field (e.g. liver) might possess a discontinuous dose profile. Projection radiography and mammography involve an even higher level of organ dose heterogeneity spanning up to two orders of magnitude. As such, mean dose or point measured dose values do not reflect the maximum energy deposited per unit volume of the organ. In this paper, the magnitude of the dose heterogeneity in both CT and projection X-ray imaging was reported, using Monte Carlo methods. The lung dose demonstrated factors of 1.7 and 2.2 difference between the mean and maximum dose for chest CT and radiography, respectively. The corresponding values for the liver were 1.9 and 3.5. For mammography and breast tomosynthesis, the difference between mean glandular dose and maximum glandular dose was 3.1. Risk models based on the mean dose were found to provide a reasonable reflection of cancer risk. However, for leukaemia, they were found to significantly under-represent the risk when the organ dose distribution is heterogeneous. A systematic study is needed to develop a risk model for heterogeneous dose distributions.

Uracil-ftorafur: an oral fluoropyrimidine active in colorectal cancer.

PubMed

Sulkes, A; Benner, S E; Canetta, R M

1998-10-01

This review describes the early clinical development of uracil-ftorafur (UFT), an oral fluoropyrimidine, designed in 1978 by adding uracil to ftorafur. The review focuses on the treatment of colorectal cancer and summarizes the Japanese experience and the phase I and II trials performed in the United States and Europe. Clinical trials of UFT published in the Western world have included 581 patients with colorectal cancer. UFT has been administered in these trials as a single agent or biomodulated by leucovorin (LV). UFT was administered daily in split doses for periods that ranged from 14 to 28 days. The activity of oral UFT in large-bowel cancer when administered with oral LV (approximately 50 mg/dose) has resulted in objective response rates of approximately 40%. Response rates of approximately 25% (range, 17% to 39%) were reported when UFT was administered as a single agent or with lower doses of LV. The highest dose-intensities of UFT are achieved with 28-day schedules of administration. The maximum-tolerated dose (MTD) of UFT with this schedule, when administered concomitantly with oral LV 150 mg daily, is 300 mg/m2 daily. The dose-limiting toxicity (DLT) of UFT has generally been diarrhea. Other commonly described toxicities include nausea and vomiting, fatigue, and stomatitis. Myelosuppression occurs infrequently. Typically, hand-foot syndrome and neurologic toxicity are lacking. UFT is a fluoropyrimidine active in colorectal cancer. The oral route of administration and improved safety profile represent important advantages over both conventional and infusional fluorouracil (5-FU) regimens.

Main Sources and Doses of Space Radiation during Mars Missions and Total Radiation Risk for Cosmonauts

NASA Astrophysics Data System (ADS)

Mitrikas, Victor; Aleksandr, Shafirkin; Shurshakov, Vyacheslav

This work contains calculation data of generalized doses and dose equivalents in critical organs and tissues of cosmonauts produces by galactic cosmic rays (GCR), solar cosmic rays (SCR) and the Earth’s radiation belts (ERB) that will impact crewmembers during a flight to Mars, while staying in the landing module and on the Martian surface, and during the return to Earth. Also calculated total radiation risk values during whole life of cosmonauts after the flight are presented. Radiation risk (RR) calculations are performed on the basis of a radiobiological model of radiation damage to living organisms, while taking into account reparation processes acting during continuous long-term exposure at various dose rates and under acute recurrent radiation impact. The calculations of RR are performed for crewmembers of various ages implementing a flight to Mars over 2 - 3 years in maximum and minimum of the solar cycle. The total carcinogenic and non-carcinogenic RR and possible life-span shortening are estimated on the basis of a model of the radiation death probability for mammals. This model takes into account the decrease in compensatory reserve of an organism as well as the increase in mortality rate and descent of the subsequent lifetime of the cosmonaut. The analyzed dose distributions in the shielding and body areas are applied to making model calculations of tissue equivalent spherical and anthropomorphic phantoms.

Investigation of Natural Radioactivity in a Monazite Processing Plant in Japan.

PubMed

Iwaoka, Kazuki; Yajima, Kazuaki; Suzuki, Toshikazu; Yonehara, Hidenori; Hosoda, Masahiro; Tokonami, Shinji; Kanda, Reiko

2017-09-01

Monazite is a naturally occurring radioactive material that is processed for use in a variety of domestic applications. At present, there is little information available on potential radiation doses experienced by people working with monazite. The ambient dose rate and activity concentration of natural radionuclides in raw materials, products, and dust in work sites as well as the Rn and Rn concentrations in work sites were measured in a monazite processing plant in Japan. Dose estimations for plant workers were also conducted. The activity concentration of the U series in raw materials and products for the monazite processing plant was found to be higher than the relevant values described in the International Atomic Energy Agency Safety Standards. The ambient dose rates in the raw material yard were higher than those in other work sites. Moreover, the activity concentrations of dust in the milling site were higher than those in other work sites. The Rn concentrations in all work sites were almost the same as those in regular indoor environments in Japan. The Rn concentrations in all work sites were much higher than those in regular indoor environments in Japan. The maximum value of the effective dose for workers was 0.62 mSv y, which is lower than the reference level range (1-20 mSv y) for abnormally high levels of natural background radiation published in the International Commission of Radiological Protection Publication 103.

Opicapone: a short lived and very long acting novel catechol-O-methyltransferase inhibitor following multiple dose administration in healthy subjects

PubMed Central

Rocha, José Francisco; Almeida, Luis; Falcão, Amílcar; Palma, P Nuno; Loureiro, Ana I; Pinto, Roberto; Bonifácio, Maria João; Wright, Lyndon C; Nunes, Teresa; Soares-da-Silva, Patrício

2013-01-01

Aims The aim of this study was to assess the tolerability, pharmacokinetics and inhibitory effect on erythrocyte soluble catechol-O-methyltransferase (S-COMT) activity following repeated doses of opicapone. Methods This randomized, placebo-controlled, double-blind study enrolled healthy male subjects who received either once daily placebo or opicapone 5, 10, 20 or 30 mg for 8 days. Results Opicapone was well tolerated. Its systemic exposure increased in an approximately dose-proportional manner with an apparent terminal half-life of 1.0 to 1.4 h. Sulphation was the main metabolic pathway. Opicapone metabolites recovered in urine accounted for less than 3% of the amount of opicapone administered suggesting that bile is likely the main route of excretion. Maximum S-COMT inhibition (Emax) ranged from 69.9% to 98.0% following the last dose of opicapone. The opicapone-induced S-COMT inhibition showed a half-life in excess of 100 h, which was dose-independent and much longer than plasma drug exposure. Such a half-life translates into a putative underlying rate constant that is comparable with the estimated dissociation rate constant of the COMT–opicapone complex. Conclusion Despite its short elimination half-life, opicapone markedly and sustainably inhibited erythrocyte S-COMT activity making it suitable for a once daily regimen. PMID:23336248

Dose properties of a laser accelerated electron beam and prospects for clinical application.

PubMed

Kainz, K K; Hogstrom, K R; Antolak, J A; Almond, P R; Bloch, C D; Chiu, C; Fomytskyi, M; Raischel, F; Downer, M; Tajima, T

2004-07-01

Laser wakefield acceleration (LWFA) technology has evolved to where it should be evaluated for its potential as a future competitor to existing technology that produces electron and x-ray beams. The purpose of the present work is to investigate the dosimetric properties of an electron beam that should be achievable using existing LWFA technology, and to document the necessary improvements to make radiotherapy application for LWFA viable. This paper first qualitatively reviews the fundamental principles of LWFA and describes a potential design for a 30 cm accelerator chamber containing a gas target. Electron beam energy spectra, upon which our dose calculations are based, were obtained from a uniform energy distribution and from two-dimensional particle-in-cell (2D PIC) simulations. The 2D PIC simulation parameters are consistent with those reported by a previous LWFA experiment. According to the 2D PIC simulations, only approximately 0.3% of the LWFA electrons are emitted with an energy greater than 1 MeV. We studied only the high-energy electrons to determine their potential for clinical electron beams of central energy from 9 to 21 MeV. Each electron beam was broadened and flattened by designing a dual scattering foil system to produce a uniform beam (103%>off-axis ratio>95%) over a 25 x 25 cm2 field. An energy window (deltaE) ranging from 0.5 to 6.5 MeV was selected to study central-axis depth dose, beam flatness, and dose rate. Dose was calculated in water at a 100 cm source-to-surface distance using the EGS/BEAM Monte Carlo algorithm. Calculations showed that the beam flatness was fairly insensitive to deltaE. However, since the falloff of the depth-dose curve (R10-R90) and the dose rate both increase with deltaE, a tradeoff between minimizing (R10-R90) and maximizing dose rate is implied. If deltaE is constrained so that R10-R90 is within 0.5 cm of its value for a monoenergetic beam, the maximum practical dose rate based on 2D PIC is approximately 0.1 Gy min(-1) for a 9 MeV beam and 0.03 Gy min(-1) for a 15 MeV beam. It was concluded that current LWFA technology should allow a table-top terawatt (T3) laser to produce therapeutic electron beams that have acceptable flatness, penetration, and falloff of depth dose; however, the dose rate is still 1%-3% of that which would be acceptable, especially for higher-energy electron beams. Further progress in laser technology, e.g., increasing the pulse repetition rate or number of high energy electrons generated per pulse, is necessary to give dose rates acceptable for electron beams. Future measurements confirming dosimetric calculations are required to substantiate our results. In addition to achieving adequate dose rate, significant engineering developments are needed for this technology to compete with current electron acceleration technology. Also, the functional benefits of LWFA electron beams require further study and evaluation.

SU-F-T-673: Effects of Cardiac Induced Brain Pulsations On Proton Minibeams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eagle, J; Marsh, S; Lee, E

Purpose: To quantify the dosimetric impact of internal motion within the brain on spatially modulated proton minibeam radiation therapy (pMRT) for small animal research. Methods: The peak-to-valley dose ratio (PVDR) is an essential dosimetric factor for pMRT. Motion of an animal brain caused by cardiac-induced pulsations (CIP) can impact dose deposition. For synchrotron generated high dose rate X-ray microbeams this effect is evaded due to the quasi-instantaneous delivery. By comparison, pMRT potentially suffers increased spread due to lower dose rates. However, for a given dose rate it is less susceptible to beam spread than microbeams, due to the spatial modulationmore » being an order of magnitude larger. Monte Carlo simulations in TOPAS were used to model the beam spread for a 50.5MeV pMRT beam. Motion effects were simulated for a 50mm thick brass collimator with 0.3mm slit width and 1.0mm center-to-center spacing in a water phantom. The maximum motion in a rat brain due to CIP has been reported to be 0.06mm. Motion was simulated with a peak amplitude in the range 0–0.2mm. Results: The impact of 0.06mm peak motion was minimal and reduced the PVDR by about 1% at a depth of 10mm. For 0.2mm peak motion the PVDR was reduced by 16% at a depth of 10mm. Conclusion: For the pMRT beam the magnitude of cardiac-induced brain motion has minimal impact on the PVDR for the investigated collimator geometry. For more narrow beams the effect is likely to be larger. This indicates that delivery of pMRT to small animal brains should not be affected considerably by beamlines with linac compatible dose rates.« less

An analytic linear accelerator source model for GPU-based Monte Carlo dose calculations.

PubMed

Tian, Zhen; Li, Yongbao; Folkerts, Michael; Shi, Feng; Jiang, Steve B; Jia, Xun

2015-10-21

Recently, there has been a lot of research interest in developing fast Monte Carlo (MC) dose calculation methods on graphics processing unit (GPU) platforms. A good linear accelerator (linac) source model is critical for both accuracy and efficiency considerations. In principle, an analytical source model should be more preferred for GPU-based MC dose engines than a phase-space file-based model, in that data loading and CPU-GPU data transfer can be avoided. In this paper, we presented an analytical field-independent source model specifically developed for GPU-based MC dose calculations, associated with a GPU-friendly sampling scheme. A key concept called phase-space-ring (PSR) was proposed. Each PSR contained a group of particles that were of the same type, close in energy and reside in a narrow ring on the phase-space plane located just above the upper jaws. The model parameterized the probability densities of particle location, direction and energy for each primary photon PSR, scattered photon PSR and electron PSR. Models of one 2D Gaussian distribution or multiple Gaussian components were employed to represent the particle direction distributions of these PSRs. A method was developed to analyze a reference phase-space file and derive corresponding model parameters. To efficiently use our model in MC dose calculations on GPU, we proposed a GPU-friendly sampling strategy, which ensured that the particles sampled and transported simultaneously are of the same type and close in energy to alleviate GPU thread divergences. To test the accuracy of our model, dose distributions of a set of open fields in a water phantom were calculated using our source model and compared to those calculated using the reference phase-space files. For the high dose gradient regions, the average distance-to-agreement (DTA) was within 1 mm and the maximum DTA within 2 mm. For relatively low dose gradient regions, the root-mean-square (RMS) dose difference was within 1.1% and the maximum dose difference within 1.7%. The maximum relative difference of output factors was within 0.5%. Over 98.5% passing rate was achieved in 3D gamma-index tests with 2%/2 mm criteria in both an IMRT prostate patient case and a head-and-neck case. These results demonstrated the efficacy of our model in terms of accurately representing a reference phase-space file. We have also tested the efficiency gain of our source model over our previously developed phase-space-let file source model. The overall efficiency of dose calculation was found to be improved by ~1.3-2.2 times in water and patient cases using our analytical model.

Dose and Dose Risk Caused by Natural Phenomena - Proposed Powder Metallurgy Core Manufacturing Facility

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holmes, W.G.

2001-08-16

The offsite radiological effects from high velocity straight winds, tornadoes, and earthquakes have been estimated for a proposed facility for manufacturing enriched uranium fuel cores by powder metallurgy. Projected doses range up to 30 mrem/event to the maximum offsite individual for high winds and up to 85 mrem/event for very severe earthquakes. Even under conservative assumptions on meteorological conditions, the maximum offsite dose would be about 20 per cent of the DOE limit for accidents involving enriched uranium storage facilities. The total dose risk is low and is dominated by the risk from earthquakes. This report discusses this test.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vandervoort, E.; Szanto, J.; Christiansen, E.

Plastic scintillation dosimeters (PSDs) have favourable characteristics for small and composite field dosimetry in radiosurgery, however, imperfect corrections for the Cerenkov radiation contamination could limit their accuracy for complex deliveries. In this work, we characterize the dose and dose-rate linearity, directional dependence, and compare output factors with other stereotactic detectors for a new commercially available PSD (Exradin W1). We provide some preliminary comparisons of planned and measured dose for composite fields delivered clinically by a Cyberknife radiosurgery system. The W1 detector shows good linearity with dose (<0.5%) and dose rate (<0.8%) relative to the signal obtained using an ion chambermore » under the same conditions. A maximum difference of 2% was observed depending on the detector's angular orientation. Output factors for all detectors agree within a range of ±3.2% and ±1.5% for the 5 and 7.5 mm collimators, respectively, provided Monte-Carlo corrections for detector effects are applied to diode and ion chambers (without corrections the range is ±5.5% and ±3.1% for these two collimators). For clinical beam deliveries using 5 and 7.5 mm collimators, four of the six patients showed better agreement with planned dose for the PSD detector compared to a micro ion chamber. Two of the six patients investigated, however, showed 5% differences between PSD and planned dose, film measurements and the ratio of PSD and micro ion chamber signal suggest that further investigation is warranted for these plans. The W1 detector is a promising tool for stereotactic plan verification under the challenging dosimetric conditions of stereotactic radiosurgery.« less

Dosimetric properties of a proton beamline dedicated to the treatment of ocular disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Slopsema, R. L., E-mail: rslopsema@floridaproton.org; Mamalui, M.; Yeung, D.

2014-01-15

Purpose: A commercial proton eyeline has been developed to treat ocular disease. Radiotherapy of intraocular lesions (e.g., uveal melanoma, age-related macular degeneration) requires sharp dose gradients to avoid critical structures like the macula and optic disc. A high dose rate is needed to limit patient gazing times during delivery of large fractional dose. Dose delivery needs to be accurate and predictable, not in the least because current treatment planning algorithms have limited dose modeling capabilities. The purpose of this paper is to determine the dosimetric properties of a new proton eyeline. These properties are compared to those of existing systemsmore » and evaluated in the context of the specific clinical requirements of ocular treatments. Methods: The eyeline is part of a high-energy, cyclotron-based proton therapy system. The energy at the entrance of the eyeline is 105 MeV. A range modulator (RM) wheel generates the spread-out Bragg peak, while a variable range shifter system adjusts the range and spreads the beam laterally. The range can be adjusted from 0.5 up to 3.4 g/cm{sup 2}; the modulation width can be varied in steps of 0.3 g/cm{sup 2} or less. Maximum field diameter is 2.5 cm. All fields can be delivered with a dose rate of 30 Gy/min or more. The eyeline is calibrated according to the IAEA TRS-398 protocol using a cylindrical ionization chamber. Depth dose distributions and dose/MU are measured with a parallel-plate ionization chamber; lateral profiles with radiochromic film. The dose/MU is modeled as a function of range, modulation width, and instantaneous MU rate with fit parameters determined per option (RM wheel). Results: The distal fall-off of the spread-out Bragg peak is 0.3 g/cm{sup 2}, larger than for most existing systems. The lateral penumbra varies between 0.9 and 1.4 mm, except for fully modulated fields that have a larger penumbra at skin. The source-to-axis distance is found to be 169 cm. The dose/MU shows a strong dependence on range (up to 4%/mm). A linear increase in dose/MU as a function of instantaneous MU rate is observed. The dose/MU model describes the measurements with an accuracy of ±2%. Neutron dose is found to be 146 ± 102 μSv/Gy at the contralateral eye and 19 ± 13 μSv/Gy at the chest. Conclusions: Measurements show the proton eyeline meets the requirements to effectively treat ocular disease.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Slopsema, R. L., E-mail: rslopsema@floridaproton.org; Mamalui, M.; Yeung, D.

Purpose: A commercial proton eyeline has been developed to treat ocular disease. Radiotherapy of intraocular lesions (e.g., uveal melanoma, age-related macular degeneration) requires sharp dose gradients to avoid critical structures like the macula and optic disc. A high dose rate is needed to limit patient gazing times during delivery of large fractional dose. Dose delivery needs to be accurate and predictable, not in the least because current treatment planning algorithms have limited dose modeling capabilities. The purpose of this paper is to determine the dosimetric properties of a new proton eyeline. These properties are compared to those of existing systemsmore » and evaluated in the context of the specific clinical requirements of ocular treatments. Methods: The eyeline is part of a high-energy, cyclotron-based proton therapy system. The energy at the entrance of the eyeline is 105 MeV. A range modulator (RM) wheel generates the spread-out Bragg peak, while a variable range shifter system adjusts the range and spreads the beam laterally. The range can be adjusted from 0.5 up to 3.4 g/cm{sup 2}; the modulation width can be varied in steps of 0.3 g/cm{sup 2} or less. Maximum field diameter is 2.5 cm. All fields can be delivered with a dose rate of 30 Gy/min or more. The eyeline is calibrated according to the IAEA TRS-398 protocol using a cylindrical ionization chamber. Depth dose distributions and dose/MU are measured with a parallel-plate ionization chamber; lateral profiles with radiochromic film. The dose/MU is modeled as a function of range, modulation width, and instantaneous MU rate with fit parameters determined per option (RM wheel). Results: The distal fall-off of the spread-out Bragg peak is 0.3 g/cm{sup 2}, larger than for most existing systems. The lateral penumbra varies between 0.9 and 1.4 mm, except for fully modulated fields that have a larger penumbra at skin. The source-to-axis distance is found to be 169 cm. The dose/MU shows a strong dependence on range (up to 4%/mm). A linear increase in dose/MU as a function of instantaneous MU rate is observed. The dose/MU model describes the measurements with an accuracy of ±2%. Neutron dose is found to be 146 ± 102 μSv/Gy at the contralateral eye and 19 ± 13 μSv/Gy at the chest. Conclusions: Measurements show the proton eyeline meets the requirements to effectively treat ocular disease.« less

Clinical assessment of the jaw-tracking function in IMRT for a brain tumor

NASA Astrophysics Data System (ADS)

Kim, Jin-Young; Kim, Shin-Wook; Choe, Bo-Young; Suh, Tae-Suk; Park, Sung-Kwang; Jo, Sun-Mi; Oh, Won-Yong; Shin, Jung-Wook; Cho, Gyu-Seok; Nam, Sang-Hee; Chung, Jin-Beom; Kim, Jung-Ki; Lee, Young-Kyu

2015-01-01

Intensity-modulated radiotherapy (IMRT) improves dose conformity and saves critical organs. IMRT is widely used in cases of head and neck, prostate, and brain cancer due to the close location of the targets to critical structures. However, because IMRT has a larger amount of radiation exposure than 3 dimensional-conformal radiation therapy (3D-CRT), it has disadvantages such as increases in the low dose irradiation to normal tissues and in the accumulated dose for the whole volume due to leakage and transmission of the multi-leaf collimator (MLC). The increased accumulated dose and the larger low dose may increase the occurrence of secondary malignant neoplasms. For these reasons, the jaw-tracking function of the TrueBeam (Varian Medical Systems, Palo Alto, CA) was developed to reduce the leakage and the transmission dose of the MLC with linear accelerators. However, the change in the superficial dose has not been verified with a quantitative analysis of the dose reduction in a brain tumor. Therefore, in the present study, we intended to verify the clinical possibility of utilizing the jaw-tracking function for a brain tumor by comparing treatment plans and superficial doses. To accomplish this, we made three types of original treatment plans using Eclipse11 (Varian Medical Systems, Palo Alto, CA): 1) farther than 2 cm from the organs at risk (OAR); 2) within 2 cm of the OAR; and 3) intersecting with the OAR. Jaw-tracking treatment plans were also made with copies of the original treatment plan using Smart LMC Version 11.0.31 (Varian Medical Systems, Palo Alto, CA). A comparison between the original treatment plans and jaw-tracking treatment plans was performed using the difference of the mean dose and maximum dose to the OARs in cumulative Dose Volume Histogram (DVH). In addition, the dependencies of the effects of transmission and the scattering doses according to jaw motion were assessed through the difference in the surface doses. In the DVH comparison, a maximum dose difference of 0.4% was observed between the planning methods in the case of over 2 cm distance, and the maximum dose of 0.6% was obtained for within the 2 cm distance. For the case intersecting with the OAR, the maximum dose difference of 2.3% was achieved. According to these results, the differences in the mean doses and the maximum doses to the OARs ware larger when the OARs and the planning target volume (PTV) were closer. In addition, small differences in the surface dose measurements were observed. In the case of the inside field, the differences were under 2% of the prescription dose while the difference was under 0.1% in the case of the outside field. Therefore, treatment plans with the jaw-tracking function consistently affected the dose reduction for a brain tumor, and the clinical possibility could be verified as the surface dose was not increased.

Metabolic and skeletal effects of low and high doses of calcium acetate in patients with preterminal chronic renal failure.

PubMed

Phelps, Kenneth R; Stern, Marc; Slingerland, Alice; Heravi, Mahin; Strogatz, David S; Haqqie, Syed S

2002-01-01

Secondary hyperparathyroidism commonly evolves, as the glomerular filtration rate falls. The metabolic and skeletal effects of a possible remedy, calcium acetate, have not been studied in patients with preterminal chronic renal failure. Men with a mean creatinine clearance of approximately 30 ml/min took calcium acetate for 24 weeks at doses which provided 507 or 1,521 mg calcium/day with meals. Metabolic determinations were made at intervals of 4-8 weeks, and the bone mineral density (BMD) was measured at the beginning and at the end of the trial. The low-dose regimen produced no metabolic or skeletal effect. In subjects prescribed the high-dose regimen, the 24-hour urine phosphorus excretion fell from 0.53 mg/mg creatinine to values ranging from 0.34 to 0.41 mg/mg creatinine. The theoretical phosphorus threshold concentration rose by a maximum of 38.6%, and the serum phosphorus concentration did not change. The mean serum calcium concentration rose by a maximum of 7.2%. The mean fractional changes in parathyroid hormone and 1,25-dihydroxyvitamin D concentrations ranged from -27.0 to -39.6% and from -5.0 to -20.3%, respectively. The BMD increased at L1, L3, and L4. Calcium acetate prescribed to deliver 1,521 mg calcium/day with meals reduced parathyroid hormone and 1,25-dihydroxyvitamin D concentrations and increased lumbar BMD in men with preterminal chronic renal failure. Copyright 2002 S. Karger AG, Basel

Bioavailability in healthy adults of efavirenz capsule contents mixed with a small amount of food.

PubMed

Kaul, Sanjeev; Ji, Ping; Lu, Michael; Nguyen, Kim L; Shangguan, Tong; Grasela, Dennis

2010-02-01

The effect of mixing the contents of efavirenz capsules (sprinkles) with a small amount of food on the bioavailability and pharmacokinetics of efavirenz in healthy adults was evaluated. In a randomized, three-period, crossover study, 24 healthy adult subjects were divided equally into two groups. Group I received treatments A, B, and C, and those in group II received treatments A, D, and E. Treatment A was three efavirenz 200-mg intact capsules under fasting conditions. Treatments B, C, D, and E were three efavirenz 200-mg capsule contents mixed with two teaspoons of applesauce, grape jelly, yogurt, or infant formula, respectively. A single dose was given on days 1, 21, and 41. The steady-state mean maximum observed concentration, time of maximum observed concentration, area under the concentration-time curve (AUC) half-life, taste, and safety were assessed. The AUC after administration of a single 600-mg dose of efavirenz sprinkles mixed with two teaspoons of any of the food vehicles to healthy adults was bioequivalent to a 600-mg efavirenz dose given as intact capsules under fasting conditions. Subjects rated efavirenz mixed with grape jelly as the most palatable. Adverse events and laboratory abnormalities were similar for all treatments. The AUC of efavirenz 600 mg administered as capsule sprinkles with two teaspoons of applesauce, grape jelly, yogurt, or infant formula was bioequivalent to a single dose of efavirenz 600 mg given as intact capsules under fasting conditions in healthy adults.

Phase I/II study of sorafenib in combination with temsirolimus for recurrent glioblastoma or gliosarcoma: North American Brain Tumor Consortium study 05-02

PubMed Central

Lee, Eudocia Q.; Kuhn, John; Lamborn, Kathleen R.; Abrey, Lauren; DeAngelis, Lisa M.; Lieberman, Frank; Robins, H. Ian; Chang, Susan M.; Yung, W. K. Alfred; Drappatz, Jan; Mehta, Minesh P.; Levin, Victor A.; Aldape, Kenneth; Dancey, Janet E.; Wright, John J.; Prados, Michael D.; Cloughesy, Timothy F.; Gilbert, Mark R.; Wen, Patrick Y.

2012-01-01

The activity of single-agent targeted molecular therapies in glioblastoma has been limited to date. The North American Brain Tumor Consortium examined the safety, pharmacokinetics, and efficacy of combination therapy with sorafenib, a small molecule inhibitor of Raf, vascular endothelial growth factor receptor 2, and platelet-derived growth factor receptor–β, and temsirolimus (CCI-779), an inhibitor of mammalian target of rapamycin. This was a phase I/II study. The phase I component used a standard 3 × 3 dose escalation scheme to determine the safety and tolerability of this combination therapy. The phase II component used a 2-stage design; the primary endpoint was 6-month progression-free survival (PFS6) rate. Thirteen patients enrolled in the phase I component. The maximum tolerated dosage (MTD) for combination therapy was sorafenib 800 mg daily and temsirolimus 25 mg once weekly. At the MTD, grade 3 thrombocytopenia was the dose-limiting toxicity. Eighteen patients were treated in the phase II component. At interim analysis, the study was terminated and did not proceed to the second stage. No patients remained progression free at 6 months. Median PFS was 8 weeks. The toxicity of this combination therapy resulted in a maximum tolerated dose of temsirolimus that was only one-tenth of the single-agent dose. Minimal activity in recurrent glioblastoma multiforme was seen at the MTD of the 2 combined agents. PMID:23099651

Positive inotropic and vasodilator actions of milrinone in patients with severe congestive heart failure. Dose-response relationships and comparison to nitroprusside.

PubMed Central

Jaski, B E; Fifer, M A; Wright, R F; Braunwald, E; Colucci, W S

1985-01-01

Milrinone is a potent positive inotropic and vascular smooth muscle-relaxing agent in vitro, and therefore, it is not known to what extent each of these actions contributes to the drug's hemodynamic effects in patients with heart failure. In 11 patients with New York Heart Association class III or IV congestive heart failure, incremental intravenous doses of milrinone were administered to determine the dose-response relationships for heart rate, systemic vascular resistance, and inotropic state, the latter measured by peak positive left ventricular derivative of pressure with respect to time (dP/dt). To clarify further the role of a positive inotropic action, the relative effects of milrinone and nitroprusside on left ventricular stroke work and dP/dt were compared in each patient at doses matched to cause equivalent reductions in mean arterial pressure or systemic vascular resistance, indices of left ventricular afterload. Milrinone caused heart rate, stroke volume, and dP/dt to increase, and systemic vascular resistance to decrease in a concentration-related manner. At the two lowest milrinone doses resulting in serum concentrations of 63 +/- 4 and 156 +/- 5 ng/ml, respectively, milrinone caused significant increases in stroke volume and dP/dt, but no changes in systemic vascular resistance or heart rate. At the maximum milrinone dose administered (mean serum concentration, 427 +/- 11 ng/ml), heart rate increased from 92 +/- 4 to 99 +/- 4 bpm (P less than 0.01), mean aortic pressure fell from 82 +/- 3 to 71 +/- 3 mmHg (P less than 0.01), right atrial pressure fell from 15 +/- 2 to 7 +/- 1 mmHg (P less than 0.005), left ventricular end-diastolic pressure fell from 26 +/- 3 to 18 +/- 3 (P less than 0.005), stroke volume index increased from 20 +/- 2 to 30 +/- 2 ml/m2 (P less than 0.005), stroke work index increased from 14 +/- 2 to 21 +/- 2 g X m/m2 (P less than 0.01), and dP/dt increased from 858 +/- 54 to 1,130 +/- 108 mmHg/s (P less than 0.005). When compared with nitroprusside for a matched reduction in mean aortic pressure or systemic vascular resistance, milrinone caused a significantly greater increase in stroke work index at the same or lower left ventricular end-diastolic pressure. Milrinone caused a concentration-related increase in dP/dt (32% increase at maximum milrinone dose), whereas nitroprusside had no effect. These data in patients with severe heart failure indicate that in addition to a vasodilating effect, milrinone exerts a concentration-related positive inotropic action that contributes significantly to the drug's overall hemodynamic effects. The positive inotropic action occurs at drug levels that do not exert significant chronotropic or vasodilator effects. Images PMID:3973022

Key parameters and practices controlling pesticide degradation efficiency of biobed substrates.

PubMed

Karanasios, Evangelos; Karpouzas, Dimitrios G; Tsiropoulos, Nikolaos G

2012-01-01

We studied the contribution of each of the components of a compost-based biomixture (BX), commonly used in Europe, on pesticide degradation. The impact of other key parameters including pesticide dose, temperature and repeated applications on the degradation of eight pesticides, applied as a mixture, in a BX and a peat-based biomixture (OBX) was compared and contrasted to their degradation in soil. Incubation studies showed that straw was essential in maintaining a high pesticide degradation capacity of the biomixture, whereas compost, when mixed with soil, retarded pesticide degradation. The highest rates of degradation were shown in the biomixture composed of soil/compost/straw suggesting that all three components are essential for maximum biobed performance. Increasing doses prolonged the persistence of most pesticides with biomixtures showing a higher tolerance to high pesticide dose levels compared to soil. Increasing the incubation temperature from 15 °C to 25 °C resulted in lower t(1/2) values, with biomixtures performing better than soil at the lower temperature. Repeated applications led to a decrease in the degradation rates of most pesticides in all the substrates, with the exception of iprodione and metalaxyl. Overall, our results stress the ability of biomixtures to perform better than soil under unfavorable conditions and extreme pesticide dose levels. Copyright © Taylor & Francis Group, LLC

Tribological characteristics of nitrogen (N+) implanted iron

NASA Technical Reports Server (NTRS)

Jones, W. R.; Ferrante, J.

1982-01-01

The effect of implantation of nitrogen ions (1.5 MeV) on the friction and wear characteristics of pure ion sliding against M-50 steel (unimplanted) was studied in a pin-on-disk sliding friction apparatus. Test conditions included room temperature (25 C), a dry air atmosphere, a load of 1/2 kg (4.9 N), sliding velocities of 0.043 to 0.078 m/sec (15 to 25 rpm), a pure hydrocarbon lubricant (n-hexadecane), or a U.S.P. mineral oil and nitrogen ion implantation doses of 5x10 to the 15th power and 5x10 to the 17th power ions/sq cm. No differences in wear rates were observed in the low dose experiments. In the high dose experiments, small reductions in initial (40 percent) and steady state (20 percent) wear rates were observed for nitrogen implanted iron riders as compared with unimplanted controls. No differences in average friction coefficients were noted for either dose. Auger electron spectroscopy combined with argon ion bombardment revealed a subsurface Gaussian nitrogen distribution with a maximum concentration of 6 atomic percent at a depth of 0.8 microns. Similar analysis within the wear scar of an implanted rider after 20 microns of wear yielded only background nitrogen concentration. No inward migration of nitrogen ions was observed.

A Phase I/II Trial of Intensity Modulated Radiation (IMRT) Dose Escalation With Concurrent Fixed-dose Rate Gemcitabine (FDR-G) in Patients With Unresectable Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ben-Josef, Edgar, E-mail: edgar.ben-josef@uphs.upenn.edu; Schipper, Mathew; Francis, Isaac R.

2012-12-01

Purpose: Local failure in unresectable pancreatic cancer may contribute to death. We hypothesized that intensification of local therapy would improve local control and survival. The objectives were to determine the maximum tolerated radiation dose delivered by intensity modulated radiation with fixed-dose rate gemcitabine (FDR-G), freedom from local progression (FFLP), and overall survival (OS). Methods and Materials: Eligibility included pathologic confirmation of adenocarcinoma, radiographically unresectable, performance status of 0-2, absolute neutrophil count of {>=}1500/mm{sup 3}, platelets {>=}100,000/mm{sup 3}, creatinine <2 mg/dL, bilirubin <3 mg/dL, and alanine aminotransferase/aspartate aminotransferase {<=}2.5 Multiplication-Sign upper limit of normal. FDR-G (1000 mg/m{sup 2}/100 min intravenously) wasmore » given on days -22 and -15, 1, 8, 22, and 29. Intensity modulated radiation started on day 1. Dose levels were escalated from 50-60 Gy in 25 fractions. Dose-limiting toxicity was defined as gastrointestinal toxicity grade (G) {>=}3, neutropenic fever, or deterioration in performance status to {>=}3 between day 1 and 126. Dose level was assigned using TITE-CRM (Time-to-Event Continual Reassessment Method) with the target dose-limiting toxicity (DLT) rate set to 0.25. Results: Fifty patients were accrued. DLTs were observed in 11 patients: G3/4 anorexia, nausea, vomiting, and/or dehydration (7); duodenal bleed (3); duodenal perforation (1). The recommended dose is 55 Gy, producing a probability of DLT of 0.24. The 2-year FFLP is 59% (95% confidence interval [CI]: 32-79). Median and 2-year overall survival are 14.8 months (95% CI: 12.6-22.2) and 30% (95% CI 17-45). Twelve patients underwent resection (10 R0, 2 R1) and survived a median of 32 months. Conclusions: High-dose radiation therapy with concurrent FDR-G can be delivered safely. The encouraging efficacy data suggest that outcome may be improved in unresectable patients through intensification of local therapy.« less

Induction and concurrent chemotherapy with high-dose thoracic conformal radiation therapy in unresectable stage IIIA and IIIB non-small-cell lung cancer: a dose-escalation phase I trial.

PubMed

Socinski, Mark A; Morris, David E; Halle, Jan S; Moore, Dominic T; Hensing, Thomas A; Limentani, Steven A; Fraser, Robert; Tynan, Maureen; Mears, Andrea; Rivera, M Patricia; Detterbeck, Frank C; Rosenman, Julian G

2004-11-01

Local control rates at conventional radiotherapy doses (60 to 66 Gy) are poor in stage III non-small-cell lung cancer (NSCLC). Dose escalation using three-dimensional thoracic conformal radiation therapy (TCRT) is one strategy to improve local control and perhaps survival. Stage III NSCLC patients with a good performance status (PS) were treated with induction chemotherapy (carboplatin area under the curve [AUC] 5, irinotecan 100 mg/m(2), and paclitaxel 175 mg/m(2) days 1 and 22) followed by concurrent chemotherapy (carboplatin AUC 2 and paclitaxel 45 mg/m(2) weekly for 7 to 8 weeks) beginning on day 43. Pre- and postchemotherapy computed tomography scans defined the initial clinical target volume (CTV(I)) and boost clinical target volume (CTV(B)), respectively. The CTV(I) received 40 to 50 Gy; the CTV(B) received escalating doses of TCRT from 78 Gy to 82, 86, and 90 Gy. The primary objective was to escalate the TCRT dose from 78 to 90 Gy or to the maximum-tolerated dose. Twenty-nine patients were enrolled (25 assessable patients; median age, 59 years; 62% male; 45% stage IIIA; 38% PS 0; and 38% > or = 5% weight loss). Induction CIP was well tolerated (with filgrastim support) and active (partial response rate, 46.2%; stable disease, 53.8%; and early progression, 0%). The TCRT dose was escalated from 78 to 90 Gy without dose-limiting toxicity. The primary acute toxicity was esophagitis (16%, all grade 3). Late toxicity consisted of grade 2 esophageal stricture (n = 3), bronchial stenosis (n = 2), and fatal hemoptysis (n = 2). The overall response rate was 60%, with a median survival time and 1-year survival probability of 24 months and 0.73 (95% CI, 0.55 to 0.89), respectively. CONCLUSION Escalation of the TCRT dose from 78 to 90 Gy in the context of induction and concurrent chemotherapy was accomplished safely in stage III NSCLC patients.

Developability assessment of clinical drug products with maximum absorbable doses.

PubMed

Ding, Xuan; Rose, John P; Van Gelder, Jan

2012-05-10

Maximum absorbable dose refers to the maximum amount of an orally administered drug that can be absorbed in the gastrointestinal tract. Maximum absorbable dose, or D(abs), has proved to be an important parameter for quantifying the absorption potential of drug candidates. The purpose of this work is to validate the use of D(abs) in a developability assessment context, and to establish appropriate protocol and interpretation criteria for this application. Three methods for calculating D(abs) were compared by assessing how well the methods predicted the absorption limit for a set of real clinical candidates. D(abs) was calculated for these clinical candidates by means of a simple equation and two computer simulation programs, GastroPlus and an program developed at Eli Lilly and Company. Results from single dose escalation studies in Phase I clinical trials were analyzed to identify the maximum absorbable doses for these compounds. Compared to the clinical results, the equation and both simulation programs provide conservative estimates of D(abs), but in general D(abs) from the computer simulations are more accurate, which may find obvious advantage for the simulations in developability assessment. Computer simulations also revealed the complex behavior associated with absorption saturation and suggested in most cases that the D(abs) limit is not likely to be achieved in a typical clinical dose range. On the basis of the validation findings, an approach is proposed for assessing absorption potential, and best practices are discussed for the use of D(abs) estimates to inform clinical formulation development strategies. Copyright © 2012 Elsevier B.V. All rights reserved.

Individual dose adjustment of riociguat in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.

PubMed

Hill, Nicholas S; Rahaghi, Franck F; Sood, Namita; Frey, Reiner; Ghofrani, Hossein-Ardeschir

2017-08-01

Riociguat is a soluble guanylate cyclase stimulator that has been approved for the treatment of pulmonary arterial hypertension and inoperable chronic thromboembolic pulmonary hypertension or persistent/recurrent pulmonary hypertension following pulmonary endarterectomy. Riociguat is administered using an 8-week individual dose-adjustment scheme whereby a patient initially receives riociguat 1.0 mg three times daily (tid), and the dose is then increased every 2 weeks in the absence of hypotension, indicated by systolic blood pressure measurements and symptoms, up to a maximum dose of 2.5 mg tid. The established riociguat dose-adjustment scheme allows the dose of riociguat to be individually optimized in terms of tolerability and efficacy. The majority of patients in the phase III clinical trials and their long-term extension phases achieved the maximum riociguat dose, whereas some patients remained on lower doses. There is evidence that these patients may experience benefits at riociguat doses lower than 2.5 mg tid, with improvement in exercise capacity being observed after only 2-4 weeks of treatment in the phase III studies and in the exploratory 1.5 mg-maximum patient group of PATENT-1. This review aims to provide an overview of the rationale behind the riociguat dose-adjustment scheme and examine its application to both clinical trials and real-life clinical practice. Copyright © 2017 Elsevier Ltd. All rights reserved.

Multileaf collimator tongue-and-groove effect on depth and off-axis doses: A comparison of treatment planning data with measurements and Monte Carlo calculations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Hee Jung; Department of Biomedical Engineering, Seoul National University, Seoul; Department of Radiation Oncology, Soonchunhyang University Hospital, Seoul

2015-01-01

To investigate how accurately treatment planning systems (TPSs) account for the tongue-and-groove (TG) effect, Monte Carlo (MC) simulations and radiochromic film (RCF) measurements were performed for comparison with TPS results. Two commercial TPSs computed the TG effect for Varian Millennium 120 multileaf collimator (MLC). The TG effect on off-axis dose profile at 3 depths of solid water was estimated as the maximum depth and the full width at half maximum (FWHM) of the dose dip at an interleaf position. When compared with the off-axis dose of open field, the maximum depth of the dose dip for MC and RCF rangedmore » from 10.1% to 20.6%; the maximum depth of the dose dip gradually decreased by up to 8.7% with increasing depths of 1.5 to 10 cm and also by up to 4.1% with increasing off-axis distances of 0 to 13 cm. However, TPS results showed at most a 2.7% decrease for the same depth range and a negligible variation for the same off-axis distances. The FWHM of the dose dip was approximately 0.19 cm for MC and 0.17 cm for RCF, but 0.30 cm for Eclipse TPS and 0.45 cm for Pinnacle TPS. Accordingly, the integrated value of TG dose dip for TPS was larger than that for MC and RCF and almost invariant along the depths and off-axis distances. We concluded that the TG dependence on depth and off-axis doses shown in the MC and RCF results could not be appropriately modeled by the TPS versions in this study.« less

Confusion: acetaminophen dosing changes based on NO evidence in adults.

PubMed

Krenzelok, Edward P; Royal, Mike A

2012-06-01

Acetaminophen (paracetamol) plays a vital role in American health care, with in excess of 25 billion doses being used annually as a nonprescription medication. Over 200 million acetaminophen-containing prescriptions, usually in combination with an opioid, are dispensed annually. While acetaminophen is recognized as a safe and effective analgesic and antipyretic, it is also associated with significant morbidity and mortality (hepatotoxicity) if doses in excess of the therapeutic amount are ingested inappropriately. The maximum daily therapeutic dose of 3900-4000 mg was established in separate actions in 1977 and 1988, respectively, via the Food and Drug Administration (FDA) monograph process for nonprescription medications. The FDA has conducted multiple advisory committee meetings to evaluate acetaminophen and its safety profile, and has suggested (but not mandated) a reduction in the maximum daily dosage from 3900-4000 mg to 3000-3250 mg. In 2011, McNeil, the producer of the Tylenol® brand of acetaminophen, voluntarily reduced the maximum daily dose of its 500 mg tablet product to 3000 mg/day, and it has pledged to change the labeling of its 325 mg/tablet product to reflect a maximum of 3250 mg/day. Generic manufacturers have not changed their dosing regimens and they have remained consistent with the established monograph dose. Therefore, confusion will be inevitable as both consumers and health care professionals try to determine the proper therapeutic dose of acetaminophen. Which is the correct dose of acetaminophen: 3000 mg if 500 mg tablets are used, 3250 mg with 325 mg tablets, or 3900 mg when 650 mg arthritis-strength products are used?

A triplet combination with capecitabine/oxaliplatin/irinotecan (XELOXIRI) plus cetuximab as first-line therapy for patients with metastatic colorectal cancer: a dose escalation study.

PubMed

Sato, Yasushi; Hirakawa, Masahiro; Ohnuma, Hiroyuki; Takahashi, Minoru; Okamoto, Tetsuro; Okamoto, Koichi; Miyamoto, Hiroshi; Muguruma, Naoki; Furuhata, Tomohisa; Takemasa, Ichiro; Kato, Junji; Takayama, Tetsuji

2017-12-01

The addition of cetuximab to triplet chemotherapy can increase treatment efficacy for patients with metastatic colorectal cancer (mCRC). We explored the dose-limiting toxicity and feasibility of a triweekly capecitabine, oxaliplatin, irinotecan, plus cetuximab (XELOXIRI plus cetuximab) regimen in patients with wild-type KRAS mCRC. Patients received oxaliplatin (100 mg/m 2 , day 1), capecitabine (1700 mg/m 2 per day from day 2 to 15), irinotecan (100, 120, and 150 mg/m 2 for dose levels 1, 2, 3, respectively, on day 1), and cetuximab (400 mg/m 2 , day 1 and, thereafter, 250 mg/m 2 every week), repeated every 3 weeks. Dose-limiting toxicities (DLTs) were assessed in the first 2 treatment cycles to determine the maximum tolerated dose (MTD) and the recommended dose (RD). Twelve patients received a median of 7 cycles of therapy (range 2-10). The DLT was grade 4 neutropenia, observed in 1 of 6 patients at dose level 2. The MTD was not reached at dose level 3. Therefore, the RD of irinotecan was defined as 150 mg/m 2 . Most common grade ≥ 3 toxicities were neutropenia (50%), diarrhea (17%), and febrile neutropenia (8%). The response rate was 83% (complete and partial response: 1 and 9 patient(s), respectively), including 4 conversion cases. The combination of XELOXIRI and cetuximab is feasible and has an acceptable toxicity profile; neutropenia was the DLT. The RD of irinotecan is 150 mg/m 2 . The observed response rate was promising and warrants further investigation.

Absence of food effect on the extent of alprazolam absorption from an orally disintegrating tablet.

PubMed

Erdman, Keith; Stypinski, Daria; Combs, Michelle; Witt, Patricia; Stiles, Mark; Pollock, Steve

2007-08-01

To evaluate the effect of a standardized meal on the bioavailability of alprazolam formulated as an immediate-release orally disintegrating tablet (ODT) in healthy volunteers. Single-dose, randomized, open-label, two-period crossover study. Contract research organization clinic. Sixteen healthy volunteers (seven men, nine women), aged 20-50 years. Intervention. Subjects were administered a single dose of alprazolam ODT 1.0 mg during two treatment periods-under fasting conditions and after a standard high-fat breakfast-separated by a 7-day washout period, Blood samples for determination of alprazolam pharmacokinetics were collected by venipuncture up to 72 hours after dosing. A validated liquid chromatography with tandem mass spectrometry detection method was used to quantify the alprazolam plasma concentration. The overall extent of alprazolam absorption from the ODT formulation, as measured by area under the concentration-time curve, was unaffected during fed conditions. However, the rate of alprazolam absorption was slower after administration during fed relative to fasted conditions. The mean maximum observed plasma concentration (Cmax) decreased approximately 25%, and time to Cmax (Tmax) was delayed approximately 1.5 hours when food was administered before dosing. Coadministration of food was shown to have no effect on extent of absorption of immediate-release alprazolam ODT 1.0 mg when compared with drug administration in the fasted condition; however, the rate of drug absorption was decreased. The clinical significance of the difference in rate of alprazolam absorption is unknown but thought to be minimal.

SU-E-T-117: Analysis of the ArcCHECK Dosimetry Gamma Failure Using the 3DVH System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cho, S; Choi, W; Lee, H

2015-06-15

Purpose: To evaluate gamma analysis failure for the VMAT patient specific QA using ArcCHECK cylindrical phantom. The 3DVH system(Sun Nuclear, FL) was used to analyze the dose difference statistic between measured dose and treatment planning system calculated dose. Methods: Four case of gamma analysis failure were selected retrospectively. Our institution gamma analysis indexes were absolute dose, 3%/3mm and 90%pass rate in the ArcCHECK dosimetry. The collapsed cone convolution superposition (CCCS) dose calculation algorithm for VMAT was used. Dose delivery was performed with Elekta Agility. The A1SL(standard imaging, WI) and cavity plug were used for point dose measurement. Delivery QA plansmore » and images were used for 3DVH Reference data instead of patient plan and image. The measured data of ‘.txt’ file was used for comparison at diodes to acquire a global dose level. The,.acml’ file was used for AC-PDP and to calculated point dose. Results: The global dose of 3DVH was calculated as 1.10 Gy, 1.13, 1.01 and 0.2 Gy respectively. The global dose of 0.2 Gy case was induced by distance discrepancy. The TPS calculated point dose of was 2.33 Gy to 2.77 Gy and 3DVH calculated dose was 2.33 Gy to 2.68 Gy. The maximum dose differences were −2.83% and −3.1% for TPS vs. measured dose and TPS vs. 3DVH calculated respectively in the same case. The difference between measured and 3DVH was 0.1% in that case. The 3DVH gamma pass rate was 98% to 99.7%. Conclusion: We found the TPS calculation error by 3DVH calculation using ArcCHECK measured dose. It seemed that our CCCS algorithm RTP system over estimated at the central region and underestimated scattering at the peripheral diode detector point. The relative gamma analysis and point dose measurement would be recommended for VMAT DQA in the gamma failure case of ArcCHECK dosimetry.« less

Optimisation techniques in vaginal cuff brachytherapy.

PubMed

Tuncel, N; Garipagaoglu, M; Kizildag, A U; Andic, F; Toy, A

2009-11-01

The aim of this study was to explore whether an in-house dosimetry protocol and optimisation method are able to produce a homogeneous dose distribution in the target volume, and how often optimisation is required in vaginal cuff brachytherapy. Treatment planning was carried out for 109 fractions in 33 patients who underwent high dose rate iridium-192 (Ir(192)) brachytherapy using Fletcher ovoids. Dose prescription and normalisation were performed to catheter-oriented lateral dose points (dps) within a range of 90-110% of the prescribed dose. The in-house vaginal apex point (Vk), alternative vaginal apex point (Vk'), International Commission on Radiation Units and Measurements (ICRU) rectal point (Rg) and bladder point (Bl) doses were calculated. Time-position optimisations were made considering dps, Vk and Rg doses. Keeping the Vk dose higher than 95% and the Rg dose less than 85% of the prescribed dose was intended. Target dose homogeneity, optimisation frequency and the relationship between prescribed dose, Vk, Vk', Rg and ovoid diameter were investigated. The mean target dose was 99+/-7.4% of the prescription dose. Optimisation was required in 92 out of 109 (83%) fractions. Ovoid diameter had a significant effect on Rg (p = 0.002), Vk (p = 0.018), Vk' (p = 0.034), minimum dps (p = 0.021) and maximum dps (p<0.001). Rg, Vk and Vk' doses with 2.5 cm diameter ovoids were significantly higher than with 2 cm and 1.5 cm ovoids. Catheter-oriented dose point normalisation provided a homogeneous dose distribution with a 99+/-7.4% mean dose within the target volume, requiring time-position optimisation.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Heng, E-mail: hengli@mdanderson.org; Zhu, X. Ronald; Zhang, Xiaodong

Purpose: To develop and validate a novel delivery strategy for reducing the respiratory motion–induced dose uncertainty of spot-scanning proton therapy. Methods and Materials: The spot delivery sequence was optimized to reduce dose uncertainty. The effectiveness of the delivery sequence optimization was evaluated using measurements and patient simulation. One hundred ninety-one 2-dimensional measurements using different delivery sequences of a single-layer uniform pattern were obtained with a detector array on a 1-dimensional moving platform. Intensity modulated proton therapy plans were generated for 10 lung cancer patients, and dose uncertainties for different delivery sequences were evaluated by simulation. Results: Without delivery sequence optimization,more » the maximum absolute dose error can be up to 97.2% in a single measurement, whereas the optimized delivery sequence results in a maximum absolute dose error of ≤11.8%. In patient simulation, the optimized delivery sequence reduces the mean of fractional maximum absolute dose error compared with the regular delivery sequence by 3.3% to 10.6% (32.5-68.0% relative reduction) for different patients. Conclusions: Optimizing the delivery sequence can reduce dose uncertainty due to respiratory motion in spot-scanning proton therapy, assuming the 4-dimensional CT is a true representation of the patients' breathing patterns.« less

Dosimetric characterization of a synthetic single crystal diamond detector in a clinical 62 MeV ocular therapy proton beam

NASA Astrophysics Data System (ADS)

Marinelli, Marco; Pompili, F.; Prestopino, G.; Verona, C.; Verona-Rinati, G.; Cirrone, G. A. P.; Cuttone, G.; La Rosa, R. M.; Raffaele, L.; Romano, F.; Tuvè, C.

2014-12-01

A synthetic single crystal diamond based Schottky photodiode was tested at INFN-LNS on the proton beam line (62 MeV) dedicated to the radiation treatment of ocular disease. The diamond detector response was studied in terms of pre-irradiation dose, linearity with dose and dose rate, and angular dependence. Depth dose curves were measured for the 62 MeV pristine proton beam and for three unmodulated range-shifted proton beams; furthermore, the spread-out Bragg peak was measured for a modulated therapeutic proton beam. Beam parameters, recommended by the ICRU report 78, were evaluated to analyze depth-dose curves from diamond detector. Measured dose distributions were compared with the corresponding dose distributions acquired with reference plane-parallel ionization chambers. Field size dependence of the output factor (dose per monitor unit) in a therapeutic modulated proton beam was measured with the diamond detector over the range of ocular proton therapy collimator diameters (5-30 mm). Output factors measured with the diamond detector were compared to the ones by a Markus ionization chamber, a Scanditronix Hi-p Si stereotactic diode and a radiochromic EBT2 film. Signal stability within 0.5% was demonstrated for the diamond detector with no need of any pre-irradiation dose. Dose and dose rate dependence of the diamond response was measured: deviations from linearity resulted to be within ±0.5% over the investigated ranges of 0.5-40.0 Gy and 0.3-30.0 Gy/min respectively. Output factors from diamond detector measured with the smallest collimator (5 mm in diameter) showed a maximum deviation of about 3% with respect to the high resolution radiochromic EBT2 film. Depth-dose curves measured by diamond for unmodulated and modulated beams were in good agreement with those from the reference plane-parallel Markus chamber, with relative differences lower than ±1% in peak-to-plateau ratios, well within experimental uncertainties. A 2.5% variation in diamond detector response was observed in angular dependence measurements carried-out by varying the proton beam incidence angle in the polar direction. The dosimetric characterization of the tested synthetic single crystal diamond detector clearly indicates its suitability for relative dosimetry in ocular therapy proton beams, with no need of any correction factors accounting for dose rate and linear energy transfer dependence.

A comparison of skin and chest wall dose delivered with multicatheter, Contura multilumen balloon, and MammoSite breast brachytherapy.

PubMed

Cuttino, Laurie W; Todor, Dorin; Rosu, Mihaela; Arthur, Douglas W

2011-01-01

Skin and chest wall doses have been correlated with toxicity in patients treated with breast brachytherapy . This investigation compared the ability to control skin and chest wall doses between patients treated with multicatheter (MC), Contura multilumen balloon (CMLB), and MammoSite (MS) brachytherapy. 43 patients treated with the MC technique, 45 patients treated with the CMLB, and 83 patients treated with the MS were reviewed. The maximum doses delivered to the skin and chest wall were calculated for all patients. The mean maximum skin doses for the MC, CMLB, and MS were 2.3 Gy (67% of prescription dose), 2.8 Gy (82% of prescription dose), and 3.2 Gy per fraction (94% of prescription dose), respectively. Although the skin distances were similar (p = 0.23) for the two balloon techniques, the mean skin dose with the CMLB was significantly lower than with the MS (p = 0.05). The mean maximum rib doses for the MC, CMLB, and MS were 2.3 Gy (67% of prescription dose), 2.8 Gy (82% of prescription dose), and 3.6 Gy per fraction (105% of prescription dose), respectively. Again, the mean rib dose with the CMLB was significantly lower than with the MS (p = 0.002). The MC and CMLB techniques are associated with significantly lower mean skin and rib doses than is the MS. Treatment with the MS was associated with significantly more patients receiving doses to the skin or rib in excess of 125% of the prescription. Treatment with the CMLB may prove to yield less normal tissue toxicity than treatment with the MS. Copyright © 2011 Elsevier Inc. All rights reserved.

A Comparison of Skin and Chest Wall Dose Delivered With Multicatheter, Contura Multilumen Balloon, and MammoSite Breast Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cuttino, Laurie W., E-mail: lcuttino@mcvh-vcu.ed; Todor, Dorin; Rosu, Mihaela

2011-01-01

Purpose: Skin and chest wall doses have been correlated with toxicity in patients treated with breast brachytherapy . This investigation compared the ability to control skin and chest wall doses between patients treated with multicatheter (MC), Contura multilumen balloon (CMLB), and MammoSite (MS) brachytherapy. Methods and Materials: 43 patients treated with the MC technique, 45 patients treated with the CMLB, and 83 patients treated with the MS were reviewed. The maximum doses delivered to the skin and chest wall were calculated for all patients. Results: The mean maximum skin doses for the MC, CMLB, and MS were 2.3 Gy (67%more » of prescription dose), 2.8 Gy (82% of prescription dose), and 3.2 Gy per fraction (94% of prescription dose), respectively. Although the skin distances were similar (p = 0.23) for the two balloon techniques, the mean skin dose with the CMLB was significantly lower than with the MS (p = 0.05). The mean maximum rib doses for the MC, CMLB, and MS were 2.3 Gy (67% of prescription dose), 2.8 Gy (82% of prescription dose), and 3.6 Gy per fraction (105% of prescription dose), respectively. Again, the mean rib dose with the CMLB was significantly lower than with the MS (p = 0.002). Conclusion: The MC and CMLB techniques are associated with significantly lower mean skin and rib doses than is the MS. Treatment with the MS was associated with significantly more patients receiving doses to the skin or rib in excess of 125% of the prescription. Treatment with the CMLB may prove to yield less normal tissue toxicity than treatment with the MS.« less

Methods for estimation of radiation risk in epidemiological studies accounting for classical and Berkson errors in doses.

PubMed

Kukush, Alexander; Shklyar, Sergiy; Masiuk, Sergii; Likhtarov, Illya; Kovgan, Lina; Carroll, Raymond J; Bouville, Andre

2011-02-16

With a binary response Y, the dose-response model under consideration is logistic in flavor with pr(Y=1 | D) = R (1+R)(-1), R = λ(0) + EAR D, where λ(0) is the baseline incidence rate and EAR is the excess absolute risk per gray. The calculated thyroid dose of a person i is expressed as Dimes=fiQi(mes)/Mi(mes). Here, Qi(mes) is the measured content of radioiodine in the thyroid gland of person i at time t(mes), Mi(mes) is the estimate of the thyroid mass, and f(i) is the normalizing multiplier. The Q(i) and M(i) are measured with multiplicative errors Vi(Q) and ViM, so that Qi(mes)=Qi(tr)Vi(Q) (this is classical measurement error model) and Mi(tr)=Mi(mes)Vi(M) (this is Berkson measurement error model). Here, Qi(tr) is the true content of radioactivity in the thyroid gland, and Mi(tr) is the true value of the thyroid mass. The error in f(i) is much smaller than the errors in ( Qi(mes), Mi(mes)) and ignored in the analysis. By means of Parametric Full Maximum Likelihood and Regression Calibration (under the assumption that the data set of true doses has lognormal distribution), Nonparametric Full Maximum Likelihood, Nonparametric Regression Calibration, and by properly tuned SIMEX method we study the influence of measurement errors in thyroid dose on the estimates of λ(0) and EAR. The simulation study is presented based on a real sample from the epidemiological studies. The doses were reconstructed in the framework of the Ukrainian-American project on the investigation of Post-Chernobyl thyroid cancers in Ukraine, and the underlying subpolulation was artificially enlarged in order to increase the statistical power. The true risk parameters were given by the values to earlier epidemiological studies, and then the binary response was simulated according to the dose-response model.

Updates from the MSL-RAD Experiment on the Mars Curiosity Rover

NASA Technical Reports Server (NTRS)

Zeitlin, Cary

2015-01-01

The MSL-RAD instrument continues to operate flawlessly on Mars. As of this writing, some 1040 sols (Martian days) of data have been successfully acquired. Several improvements have been made to the instrument's configuration, particularly aimed at enabling the analysis of neutral-particle data. The dose rate since MSL's landing in August 2012 has remained remarkably stable, reflecting the unusual and very weak solar maximum of Cycle 24. Only a few small SEP events have been observed by RAD, which is shielded by the Martian atmosphere. Gale Crater, where Curiosity landed, is 4.4 km below the mean surface of Mars, and the column depth of atmosphere above is approximately 20 g/sq cm, which provides significant attenuation of GCR heavy ions and SEPs. Recent analysis results will be presented, including updated estimates of the neutron contributions to dose and dose equivalent in cruise and on the surface of Mars.

Quantifying the impact of immediate reconstruction in postmastectomy radiation: a large, dose-volume histogram-based analysis.

PubMed

Ohri, Nisha; Cordeiro, Peter G; Keam, Jennifer; Ballangrud, Ase; Shi, Weiji; Zhang, Zhigang; Nerbun, Claire T; Woch, Katherine M; Stein, Nicholas F; Zhou, Ying; McCormick, Beryl; Powell, Simon N; Ho, Alice Y

2012-10-01

To assess the impact of immediate breast reconstruction on postmastectomy radiation (PMRT) using dose-volume histogram (DVH) data. Two hundred forty-seven women underwent PMRT at our center, 196 with implant reconstruction and 51 without reconstruction. Patients with reconstruction were treated with tangential photons, and patients without reconstruction were treated with en-face electron fields and customized bolus. Twenty percent of patients received internal mammary node (IMN) treatment. The DVH data were compared between groups. Ipsilateral lung parameters included V20 (% volume receiving 20 Gy), V40 (% volume receiving 40 Gy), mean dose, and maximum dose. Heart parameters included V25 (% volume receiving 25 Gy), mean dose, and maximum dose. IMN coverage was assessed when applicable. Chest wall coverage was assessed in patients with reconstruction. Propensity-matched analysis adjusted for potential confounders of laterality and IMN treatment. Reconstruction was associated with lower lung V20, mean dose, and maximum dose compared with no reconstruction (all P<.0001). These associations persisted on propensity-matched analysis (all P<.0001). Heart doses were similar between groups (P=NS). Ninety percent of patients with reconstruction had excellent chest wall coverage (D95 >98%). IMN coverage was superior in patients with reconstruction (D95 >92.0 vs 75.7%, P<.001). IMN treatment significantly increased lung and heart parameters in patients with reconstruction (all P<.05) but minimally affected those without reconstruction (all P>.05). Among IMN-treated patients, only lower lung V20 in those without reconstruction persisted (P=.022), and mean and maximum heart doses were higher than in patients without reconstruction (P=.006, P=.015, respectively). Implant reconstruction does not compromise the technical quality of PMRT when the IMNs are untreated. Treatment technique, not reconstruction, is the primary determinant of target coverage and normal tissue doses. Published by Elsevier Inc.

IDEAL-CRT: A Phase 1/2 Trial of Isotoxic Dose-Escalated Radiation Therapy and Concurrent Chemotherapy in Patients With Stage II/III Non-Small Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Landau, David B., E-mail: david.landau@kcl.ac.uk; Hughes, Laura; Baker, Angela

2016-08-01

Purpose: To report toxicity and early survival data for IDEAL-CRT, a trial of dose-escalated concurrent chemoradiotherapy (CRT) for non-small cell lung cancer. Patients and Methods: Patients received tumor doses of 63 to 73 Gy in 30 once-daily fractions over 6 weeks with 2 concurrent cycles of cisplatin and vinorelbine. They were assigned to 1 of 2 groups according to esophageal dose. In group 1, tumor doses were determined by an experimental constraint on maximum esophageal dose, which was escalated following a 6 + 6 design from 65 Gy through 68 Gy to 71 Gy, allowing an esophageal maximum tolerated dose to be determined from early and late toxicities. Tumormore » doses for group 2 patients were determined by other tissue constraints, often lung. Overall survival, progression-free survival, tumor response, and toxicity were evaluated for both groups combined. Results: Eight centers recruited 84 patients: 13, 12, and 10, respectively, in the 65-Gy, 68-Gy, and 71-Gy cohorts of group 1; and 49 in group 2. The mean prescribed tumor dose was 67.7 Gy. Five grade 3 esophagitis and 3 grade 3 pneumonitis events were observed across both groups. After 1 fatal esophageal perforation in the 71-Gy cohort, 68 Gy was declared the esophageal maximum tolerated dose. With a median follow-up of 35 months, median overall survival was 36.9 months, and overall survival and progression-free survival were 87.8% and 72.0%, respectively, at 1 year and 68.0% and 48.5% at 2 years. Conclusions: IDEAL-CRT achieved significant treatment intensification with acceptable toxicity and promising survival. The isotoxic design allowed the esophageal maximum tolerated dose to be identified from relatively few patients.« less

Epigenetic Therapy Using Belinostat for Patients With Unresectable Hepatocellular Carcinoma: A Multicenter Phase I/II Study With Biomarker and Pharmacokinetic Analysis of Tumors From Patients in the Mayo Phase II Consortium and the Cancer Therapeutics Research Group

PubMed Central

Yeo, Winnie; Chung, Hyun C.; Chan, Stephen L.; Wang, Ling Z.; Lim, Robert; Picus, Joel; Boyer, Michael; Mo, Frankie K.F.; Koh, Jane; Rha, Sun Y.; Hui, Edwin P.; Jeung, Hei C.; Roh, Jae K.; Yu, Simon C.H.; To, Ka F.; Tao, Qian; Ma, Brigette B.; Chan, Anthony W.H.; Tong, Joanna H.M.; Erlichman, Charles; Chan, Anthony T.C.; Goh, Boon C.

2012-01-01

Purpose Epigenetic aberrations have been reported in hepatocellular carcinoma (HCC). In this study of patients with unresectable HCC and chronic liver disease, epigenetic therapy with the histone deacetylase inhibitor belinostat was assessed. The objectives were to determine dose-limiting toxicity and maximum-tolerated dose (MTD), to assess pharmacokinetics in phase I, and to assess activity of and explore potential biomarkers for response in phase II. Patients and Methods Major eligibility criteria included histologically confirmed unresectable HCC, European Cooperative Oncology Group performance score ≤ 2, and adequate organ function. Phase I consisted of 18 patients; belinostat was given intravenously once per day on days 1 to 5 every 3 weeks; dose levels were 600 mg/m2 per day (level 1), 900 mg/m2 per day (level 2), 1,200 mg/m2 per day (level 3), and 1,400 mg/m2 per day (level 4). Phase II consisted of 42 patients. The primary end point was progression-free survival (PFS), and the main secondary end points were response according to Response Evaluation Criteria in Solid Tumors (RECIST) and overall survival (OS). Exploratory analysis was conducted on pretreatment tumor tissues to determine whether HR23B expression is a potential biomarker for response. Results Belinostat pharmacokinetics were linear from 600 to 1,400 mg/m2 without significant accumulation. The MTD was not reached at the maximum dose administered. Dose level 4 was used in phase II. The median number of cycles was two (range, one to 12). The partial response (PR) and stable disease (SD) rates were 2.4% and 45.2%, respectively. The median PFS and OS were 2.64 and 6.60 months, respectively. Exploratory analysis revealed that disease stabilization rate (complete response plus PR plus SD) in tumors having high and low HR23B histoscores were 58% and 14%, respectively (P = .036). Conclusion Epigenetic therapy with belinostat demonstrates tumor stabilization and is generally well-tolerated. HR23B expression was associated with disease stabilization. PMID:22915658

Radon survey and soil gamma doses in primary schools of Batman, Turkey.

PubMed

Damla, Nevzat; Aldemir, Kamuran

2014-06-01

A survey was conducted to evaluate levels of indoor radon and gamma doses in 42 primary schools located in Batman, southeastern Anatolia, Turkey. Indoor radon measurements were carried out using CR-39 solid-state nuclear track detector-based radon dosimeters. The overall mean annual (222)Rn activity in the surveyed area was found to be 49 Bq m(-3) (equivalent to an annual effective dose of 0.25 mSv). However, in one of the districts (Besiri) the maximum radon value turned out to be 307 Bq m(-3). The estimated annual effective doses are less than the recommended action level (3-10 mSv). It is found that the radon concentration decreases with increasing floor number. The concentrations of natural and artificial radioisotopes were determined using gamma-ray spectroscopy for soil samples collected in close vicinity of the studied schools. The mean gamma activity concentrations in the soil samples were 31, 25, 329 and 12 Bq kg(-1) for (226)Ra, (232)Th, (40)K and (137)Cs, respectively. The radiological parameters such as the absorbed dose rate in air and the annual effective dose equivalent were calculated. These radiological parameters were evaluated and compared with the internationally recommended values.

Simultaneous degradation of tetracycline and denitrification by a novel bacterium, Klebsiella sp. SQY5.

PubMed

Shao, Sicheng; Hu, Yongyou; Cheng, Ce; Cheng, Jianhua; Chen, Yuancai

2018-06-14

Polluted waters with a high residue of tetracycline also have a high concentration of nitrate. Thus, screening for both, highly efficient tetracycline biodegradation and nitrate transformation, is a key technical strategy. In this study, a novel tetracycline degrading strain, SQY5, which was identified as Klebsiella sp., was isolated from municipal sludge. Biodegradation characteristics of tetracycline were studied under various environmental conditions; including inoculation dose (v/v), initial tetracycline concentration, temperature, and pH. Response surface methodology (RSM) analysis demonstrated that the maximum degradation ratio of tetracycline can be obtained under the condition with an initial tetracycline concentration of 61.27 mg L -1 , temperature of 34.96 °C, pH of 7.17, and inoculation dose of 29.89%. Furthermore, this was the first report on the relationship between the degradation of tetracycline and the denitrification effect, showing that a maximum tetracycline reduction rate of 0.113 mg L -1 ·h -1 and denitrification rate of 4.64 mg L -1 ·h -1 were observed within 32 h and 92 h of SQY5 inoculation, respectively. The data of this study has the potential for use in engineering processes designed for the simultaneous biological removal of nitrates while degrading antibiotics. Copyright © 2018 Elsevier Ltd. All rights reserved.

SU-F-T-283: A Novel Device to Enable Portal Dosimetry for Flattening Filter Free Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Faught, A; Wu, Q; Adamson, J

Purpose: Varian’s electronic portal imaging device (EPID) based portal dosimetry tool is a popular and effective means of performing IMRT QA. EPIDs for older models of the TrueBeam accelerator utilize a 40cmx30cm Image Detection Unit (IDU) that saturates at the center for standard source to imager distances with high dose rate flattening filter free (FFF) beams. This makes portal dosimetry not possible and an alternative means of IMRT QA necessary. We developed a filter that would attenuate the beam to a dose rate measureable by the IDU for portal dosimetry IMRT QA. Methods: Multipurpose 304 stainless steel plates were placedmore » on an accessory tray to attenuate the beam. Profiles of an open field measured on the IDU were acquired with varying number of plates to assess the thickness needed to reduce the maximum dose rates of 6XFFF and 10XFFF beams to measurable levels. A new portal dose image prediction (PDIP) model was commissioned based on open field measurements with plates in position, and a modified beam profile was input to portal dosimetry calibration at the console to empirically correct for attenuation and scatter. The portal dosimetry tool was used to assess agreement between predicted and measured doses for open 25×25cm{sup 2} fields and intensity modulated fields using 6XFFF and 10XFFF beams. Results: Thicknesses of 2.5cm and 3.8cm of steel were required to reduce the highest dose rates to a measureable level for 6XFFF and 10XFFF, respectively. Gamma analysis using a 3%/3mm relative criterion with the filter in place and using the new PDIP model resulted in 98.2% and 93.6% of pixels passing while intensity modulated fields showed passing rates of 98.2% and 99.0%. Conclusion: Use of the filter allows for portal dosimetry to be used for IMRT QA of FFF plans in place of purchasing a second option for IMRT QA.« less

An open treatment trial of duloxetine in elderly patients with dysthymic disorder

PubMed Central

Kerner, Nancy; D’Antonio, Kristina; Pelton, Gregory H; Salcedo, Elianny; Ferrar, Jennifer; Roose, Steven P

2014-01-01

Objective: We evaluated the efficacy and side effects of the selective serotonin and norepinephrine reuptake inhibitor antidepressant duloxetine in older adults with dysthymic disorder. Methods: Patients ≥ 60 years old with dysthymic disorder received flexible dose duloxetine 20–120 mg daily in an open-label 12-week trial. The main outcomes were change from baseline to 12 weeks in 24-item Hamilton Depression Rating Scale scores and Treatment Emergent Symptoms Scale scores. Response required ≥ 50% decline in Hamilton Depression Rating Scale scores with a Clinical Global Impression of much improved or better, and remission required final Hamilton Depression Rating Scale ≤ 6. Intent-to-treat analyses were conducted with the last observation carried forward. Results: In 30 patients, the mean age was 70.7 (standard deviation (SD) = 7.6) years and 56.7% were female. In intent-to-treat analyses, there were 16 responders (53.3%) and 10 remitters (33.3%). Of these, 19 patients completed the trial. The mean maximum dose was 76.3 mg (SD = 38.5) in the total sample and 101 mg (SD = 17.9) in completers. In the total sample, the mean final dose was 51 mg (SD = 27.2) and correlated significantly with decline in Hamilton Depression Rating Scale (p < .03); decline in Hamilton Depression Rating Scale correlated significantly with decline in Treatment Emergent Symptoms Scale (p < .001). Daily doses above 60 mg were associated with greater improvement and well tolerated. This result was partly confounded by early dropouts having received low doses. Demographic and medical comorbidities, including cardiac disease and hypertension, were not related to response. Somatic side effects were common prior to duloxetine treatment and improved rather than worsened with duloxetine. There were no serious adverse events. Conclusion: Duloxetine at relatively high doses showed moderate efficacy in elderly patients with dysthymic disorder and was well tolerated in successful completers. Reduced somatic symptoms were associated with improvement in depressive symptoms. A systematic placebo-controlled trial of duloxetine in older patients with dysthymic disorder may be warranted. PMID:25177490

Radical radiotherapy incorporating a brachytherapy boost for the treatment of carcinoma of the thoracic oesophagus: results from a cohort of patients and review of the literature.

PubMed

Churn, M; Jones, B; Myint, A Sun

2002-04-01

The optimal treatment for potentially curable carcinoma of the oesophagus unsuitable for surgical resection is unresolved. An intraluminal brachytherapy boost (ILBT) can be used following external beam radiotherapy (EBRT) with or without concurrent chemotherapy (CRT). ILBT increases the dose to the tumour volume substantially while reducing the lung dose but the corresponding high dose to the oesophageal wall may cause increased complications. We report the outcomes of 32 consecutive patients treated with radical radiotherapy. A dose of 45-55 Gy in 20-25 fractions with external beam radiotherapy (EBRT) followed by an ILBT boost. Earlier in the series a low dose rate (LDR) brachytherapy technique using 125Iodine seeds delivering a dose of 20-22 Gy at 25-40 cGy/h was used. This was later superseded by high dose rate (HDR) treatments delivering 8.5-10 Gy in one fraction at 1 cm from the catheter. Patients of age below 76 years, of good performance status and with no other medical contraindication were considered for concurrent chemotherapy (CRT) using a planned regime of cisplatin (80 mg/m2 day 1) and 5-flurouracil (1 g/m2 days 1 to 4) in the first and last weeks of radiotherapy (13 patients). The EBRT and ILBT were well tolerated but 8/13 (62%) patients had dose modifications of chemotherapy in one or both cycles due to advanced age, co-morbidity or toxicity. The median follow-up period of surviving patients was 37 months (range 35-39) and the median overall survival for the whole group was 9 months. The overall survival at 1 year was 34.4% (17.6-51.2%), 15.6% (2.8-28.4%) at 2 and 3 years. Local recurrence-free survival at 1 year was 35.3% (15.9-54.7%) and 24.5% (8.3-44.6%) at 2 and 3 years (Fig. 2). Though symptom relief was good there were six cases of ulceration, six of stricture and two fistulae. Biological equivalent for tumour response (BED Gy,10) and late radiation effects (BED Gy3) were calculated for the different radiotherapy regimens using equations derived from the linear quadratic model. In this series no advantage was found in terms of local control or survival for patients receiving radiotherapy doses resulting in a BED Gy10 greater than 75% of the maximum. Similarly, no significant increase in complications was noted in those patients receiving doses resulting in a BED Gy3 > 75% of the maximum. The merits and hazards of the ILBT boost used in radical radiotherapy are discussed and the relevant literature reviewed.

Real world outcomes and management strategies for venetoclax-treated chronic lymphocytic leukemia patients in the United States.

PubMed

Mato, Anthony R; Thompson, Meghan; Allan, John N; Brander, Danielle M; Pagel, John M; Ujjani, Chaitra S; Hill, Brian T; Lamanna, Nicole; Lansigan, Frederick; Jacobs, Ryan; Shadman, Mazyar; Skarbnik, Alan P; Pu, Jeffrey J; Barr, Paul M; Sehgal, Alison R; Cheson, Bruce D; Zent, Clive S; Tuncer, Hande H; Schuster, Stephen J; Pickens, Peter V; Shah, Nirav N; Goy, Andre; Winter, Allison M; Garcia, Christine; Kennard, Kaitlin; Isaac, Krista; Dorsey, Colleen; Gashonia, Lisa M; Singavi, Arun K; Roeker, Lindsey E; Zelenetz, Andrew; Williams, Annalynn; Howlett, Christina; Weissbrot, Hanna; Ali, Naveed; Khajavian, Sirin; Sitlinger, Andrea; Tranchito, Eve; Rhodes, Joanna; Felsenfeld, Joshua; Bailey, Neil; Patel, Bhavisha; Burns, Timothy F; Yacur, Melissa; Malhotra, Mansi; Svoboda, Jakub; Furman, Richard R; Nabhan, Chadi

2018-06-07

Venetoclax is a BCL2 inhibitor approved for 17p-deleted relapsed/refractory chronic lymphocytic leukemia with activity following kinase inhibitors. We conducted a multicenter retrospective cohort analysis of patients with CLL treated with venetoclax to describe outcomes, toxicities, and treatment selection following venetoclax discontinuation. A total of 141 chronic lymphocytic leukemia patients were included (98% relapsed/refractory). Median age at venetoclax initiation was 67 years (range 37-91), median prior therapies was 3 (0-11), 81% unmutated IGHV, 45% del(17p), and 26.8% complex karyotype (≥ 3 abnormalities). Prior to venetoclax initiation, 89% received a B-cell receptor antagonist. For tumor lysis syndrome prophylaxis, 93% received allopurinol, 92% normal saline, and 45% rasburicase. Dose escalation to the maximum recommended dose of 400 mg daily was achieved in 85% of patients. Adverse events of interest included neutropenia in 47.4%, thrombocytopenia in 36%, tumor lysis syndrome in 13.4%, neutropenic fever in 11.6%, and diarrhea in 7.3%. The overall response rate to venetoclax was 72% (19.4% complete remission). With a median follow up of 7 months, median progression free survival and overall survival for the entire cohort have not been reached. To date, 41 venetoclax treated patients have discontinued therapy and 24 have received a subsequent therapy, most commonly ibrutinib. In the largest clinical experience of venetoclax-treated chronic lymphocytic leukemia patients , the majority successfully completed and maintained a maximum recommended dose. Response rates and duration of response appear comparable to clinical trial data. Venetoclax was active in patients with mutations known to confer ibrutinib resistance. Optimal sequencing of newer chronic lymphocytic leukemia therapies requires further study. Copyright © 2018, Ferrata Storti Foundation.

Mechanisms of inhibitory action of TRK-130 (Naltalimide), a μ-opioid receptor partial agonist, on the micturition reflex.

PubMed

Fujimura, Morihiro; Izumimoto, Naoki; Kanie, Sayoko; Kobayashi, Ryosuke; Yoshikawa, Satoru; Momen, Shinobu; Hirakata, Mikito; Komagata, Toshikazu; Okanishi, Satoshi; Iwata, Masashi; Hashimoto, Tadatoshi; Doi, Takayuki; Yoshimura, Naoki; Kawai, Koji

2017-04-01

To clarify the mechanism of inhibitory action of TRK-130 (Naltalimide), a unique µ-opioid receptor partial agonist, on the micturition reflex. The effect of TRK-130 on isovolumetric rhythmic bladder contractions (RBCs) was examined in guinea pigs, the effect of which was clarified by co-treatment with naloxone or in spinal cord transection. The effect of TRK-130 on urodynamic parameters was also observed in guinea pigs. In addition, the effect of TRK-130 on bladder contraction induced by peripheral stimulation of the pelvic nerve was investigated in rats. TRK-130 (0.001-0.01 mg/kg, iv) dose-dependently inhibited RBCs, which was dose-dependently antagonized by naloxone; however, the antagonism susceptibility was different from morphine (1 mg/kg, iv). The minimum effective dose (0.003 mg/kg) of TRK-130 remained similar in spinal cord-transected animals. TRK-130 (0.0025 mg/kg, iv) increased bladder capacity without changing the voiding efficiency, maximum flow rate, and intravesical pressure at the maximum flow rate, whereas oxybutynin (1 mg/kg, iv) increased the bladder capacity but affected the other parameters. TRK-130 (0.005 mg/kg, iv) did not produce significant changes on the bladder contractions induced by peripheral stimulation of the pelvic nerve, while oxybutynin (1 mg/kg, iv) significantly suppressed the bladder contractions. These results suggest that TRK-130 enhances the bladder storage function by modulating the afferent limb of the micturition reflex through µ-opioid receptors in the spinal cord. TRK-130 could be a more effective and safer therapeutic agent with a different fashion from antimuscarinics and conventional opioids for overactive bladder.

Evaluation of the dependence of the exposure dose on the attenuation correction in brain PET/CT scans using 18F-FDG

NASA Astrophysics Data System (ADS)

Choi, Eun-Jin; Jeong, Moon-Taeg; Jang, Seong-Joo; Choi, Nam-Gil; Han, Jae-Bok; Yang, Nam-Hee; Dong, Kyung-Rae; Chung, Woon-Kwan; Lee, Yun-Jong; Ryu, Young-Hwan; Choi, Sung-Hyun; Seong, Kyeong-Jeong

2014-01-01

This study examined whether scanning could be performed with minimum dose and minimum exposure to the patient after an attenuation correction. A Hoffman 3D Brain Phantom was used in BIO_40 and D_690 PET/CT scanners, and the CT dose for the equipment was classified as a low dose (minimum dose), medium dose (general dose for scanning) and high dose (dose with use of contrast medium) before obtaining the image at a fixed kilo-voltage-peak (kVp) and milliampere (mA) that were adjusted gradually in 17-20 stages. A PET image was then obtained to perform an attenuation correction based on an attenuation map before analyzing the dose difference. Depending on tube current in the range of 33-190 milliampere-second (mAs) when BIO_40 was used, a significant difference in the effective dose was observed between the minimum and the maximum mAs (p < 0.05). According to a Scheffe post-hoc test, the ratio of the minimum to the maximum of the effective dose was increased by approximately 5.26-fold. Depending on the change in the tube current in the range of 10-200 mA when D_690 was used, a significant difference in the effective dose was observed between the minimum and the maximum of mA (p < 0.05). The Scheffe posthoc test revealed a 20.5-fold difference. In conclusion, because effective exposure dose increases with increasing operating current, it is possible to reduce the exposure limit in a brain scan can be reduced if the CT dose can be minimized for a transmission scan.

Dose inspection and risk assessment on radiation safety for the use of non-medical X-ray machines in Taiwan

NASA Astrophysics Data System (ADS)

Hsu, Fang-Yuh; Hsu, Shih-Ming; Chao, Jiunn-Hsing

2017-11-01

The subject of this study is the on-site visits and inspections of facilities commissioned by the Atomic Energy Council (AEC) in Taiwan. This research was conducted to evaluate the possible dose and dose rate of cabinet-type X-ray equipment with nominal voltages of 30-150 kV and open-beam (portable or handheld) equipment, taking both normal operation and possibly abnormal operation conditions into account. Doses and dose rates were measured using a plastic scintillation survey meter and an electronic personal dosimeter. In total, 401 X-ray machines were inspected, including 139 units with nominal voltages of 30-50 kV X-ray equipment, 140 units with nominal voltages of 50-150 kV, and 122 open-beam (portable or handheld) X-ray equipment. The investigated doses for radiation workers and non-radiation workers operating cabinet-type X-ray equipment under normal safety conditions were all at the background dose level. Several investigated dose rates at the position of 10 cm away from the surface of open-beam (portable or handheld) X-ray equipment were very high, such X-ray machines are used by aeronautical police for the detection of suspected explosives, radiation workers are far away (at least 10 m away) from the X-ray machine during its operation. The doses per operation in X-ray equipment with a 30-50 kV nominal voltage were less than 1 mSv in all cases of abnormal use. Some doses were higher than 1 mSv per operation for X-ray equipment of 50-150 kV nominal voltage X-ray. The maximum dose rates at the beam exit have a very wide range, mostly less than 100 μSv/s and the largest value is about 3.92 mSv/s for open-beam (portable or handheld) X-ray devices. The risk induced by operating X-ray devices with nominal voltages of 30-50 kV is extremely low. The 11.5 mSv dose due to one operation at nominal voltage of 50-150 kV X-ray device is equivalent to the exposure of taking 575 chest X-rays. In the abnormal use of open-beam (portable or handheld) X-ray equipment, the effective dose of 3.92 mSv/s is equivalent to taking 196 chest radiographs within 1 s. This work assessed the annual doses (equivalent and effective doses) and risks of X-ray operator staff as reasonably as possible. The results of this research are helpful to the AEC (competent authority of ionization radiation) to improve the management and perform the safe control of X-ray equipment.

Implied Maximum Dose Analysis of Standard Values of 25 Pesticides Based on Major Human Exposure Pathways

PubMed Central

Li, Zijian; Jennings, Aaron A.

2017-01-01

Worldwide jurisdictions are making efforts to regulate pesticide standard values in residential soil, drinking water, air, and agricultural commodity to lower the risk of pesticide impacts on human health. Because human may exposure to pesticides from many ways, such as ingestion, inhalation, and dermal contact, it is important to examine pesticide standards by considering all major exposure pathways. Analysis of implied maximum dose limits for commonly historical and current used pesticides was adopted in this study to examine whether worldwide pesticide standard values are enough to prevent human health impact or not. Studies show that only U.S. has regulated pesticides standard in the air. Only 4% of the total number of implied maximum dose limits is based on three major exposures. For Chlorpyrifos, at least 77.5% of the total implied maximum dose limits are above the acceptable daily intake. It also shows that most jurisdictions haven't provided pesticide standards in all major exposures yet, and some of the standards are not good enough to protect human health. PMID:29546224

SU-E-T-548: Modeling of Breast IORT Using the Xoft 50 KV Brachytherapy Source and 316L Steel Rigid Shield

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burnside, W

Purpose: Xoft provides a set of 316L Stainless Steel Rigid Shields to be used with their 50 kV X-ray source for Breast IORT treatments. Modeling the different shield sizes in MCNP provides information to help make clinical decisions for selecting the appropriate shield size. Methods: The Xoft Axxent 50 kV Electronic Brachytherapy System has several applications in radiation therapy, one of which is treating cancer of the breast intraoperatively by placing the miniaturized X-ray tube inside an applicator balloon that is expanded to fill the lumpectomy bed immediately following tumor removal. The ribs, lung, and muscular chest wall are allmore » regions at risk to receive undesired dose during the treatment. A Xoft 316L Stainless Steel Rigid Shield can be placed between the intracostal muscles of the chest wall and the remaining breast tissue near the balloon to attenuate the beam and protect these organs. These shields are provided in 5 different sizes, and the effects on dose to the surrounding tissues vary with shield size. MCNP was used to model this environment and tally dose rate to certain regions of interest. Results: The average rib dose rate calculated using 0cm (i.e., no shield), 3cm, and 5cm diameter shields were 26.89, 15.43, and 8.91 Gy/hr respectively. The maximum dose rates within the rib reached 94.74 Gy/hr, 53.56 Gy/hr, and 31.44 Gy/hr for the 0cm, 3cm, and 5cm cases respectively. The shadowing effect caused by the steel shields was seen in the 3-D meshes and line profiles. Conclusion: This model predicts a higher dose rate to the underlying rib region with the 3cm shield compared to the 5cm shield; it may be useful to select the largest possible diameter when choosing a shield size for a particular IORT patient. The ability to attenuate the beam to reduce rib dose was also confirmed. Research sponsored by Xoft Inc, a subsidiary of iCAD.« less

Acute and sub-chronic toxicity of Cajanus cajan leaf extracts.

PubMed

Tang, Rong; Tian, Ru-Hua; Cai, Jia-Zhong; Wu, Jun-Hui; Shen, Xiao-Ling; Hu, Ying-Jie

2017-12-01

The leaves of Cajanus cajan (L.) Millsp. (Fabaceae) have diverse bioactivities, but little safety data are reported. This study examines the toxicological profiles of C. cajan leaf extracts. The leaves were extracted by water or 90% ethanol to obtain water or ethanol extract (WEC or EEC). EEC was suspended in water and successively fractionated into dichloroform and n-butanol extracts (DEC and BEC). Marker compounds of the extracts were monitored by high-performance liquid chromatography (HPLC). Kunming mice were administered with a single maximum acceptable oral dose (15.0 g/kg for WEC, EEC and BEC and 11.3 g/kg for DEC) to determine death rate or maximal tolerated doses (MTDs). In sub-chronic toxicity investigation, Sprague-Dawley rats were orally given WEC or EEC at 1.5, 3.0 or 6.0 g/kg doses for four weeks and observed for two weeks after dosing to determine toxicological symptoms, histopathology, biochemistry and haematology. Flavonoids and stilbenes in the extracts were assayed. In acute toxicity test, no mortality and noted alterations in weight and behavioural abnormality were observed, and the maximum oral doses were estimated as MTDs. In sub-chronic toxicity study, no mortality and significant variances in haematological and biochemical parameters or organ histopathology were observed, but increased kidney weight in 3.0 g/kg WEC- or 3.0 and 6.0 g/kg EEC-treated female rats, and reduced testes and epididymis weight in EEC-treated male rats were recorded. These changes returned to the level of control after recovery period. Acute and sub-chronic toxicity of Cajanus cajan leaf extracts was not observed.

Temporal Lobe Reactions After Radiotherapy With Carbon Ions: Incidence and Estimation of the Relative Biological Effectiveness by the Local Effect Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schlampp, Ingmar; Karger, Christian P.; Jaekel, Oliver

2011-07-01

Purpose: To identify predictors for the development of temporal lobe reactions (TLR) after carbon ion radiation therapy (RT) for radiation-resistant tumors in the central nervous system and to evaluate the predictions of the local effect model (LEM) used for calculation of the biologically effective dose. Methods and Materials: This retrospective study reports the TLR rates in patients with skull base chordomas and chondrosarcomas irradiated with carbon ions at GSI, Darmstadt, Germany, in the years 2002 and 2003. Calculation of the relative biological effectiveness and dose optimization of treatment plans were performed on the basis of the LEM. Clinical examinations andmore » magnetic resonance imaging (MRI) were performed at 3, 6, and 12 months after RT and annually thereafter. Local contrast medium enhancement in temporal lobes, as detected on MRI, was regarded as radiation-induced TLR. Dose-volume histograms of 118 temporal lobes in 59 patients were analyzed, and 16 therapy-associated and 2 patient-associated factors were statistically evaluated for their predictive value for the occurrence of TLR. Results: Median follow-up was 2.5 years (range, 0.3--6.6 years). Age and maximum dose applied to at least 1 cm{sup 3} of the temporal lobe (D{sub max,V-1cm}3, maximum dose in the remaining temporal lobe volume, excluding the volume 1 cm{sup 3} with the highest dose) were found to be the most important predictors for TLR. Dose response curves of D{sub max,V-1cm}3 were calculated. The biologically equivalent tolerance doses for the 5% and 50% probabilities to develop TLR were 68.8 {+-} 3.3 Gy equivalents (GyE) and 87.3 {+-} 2.8 GyE, respectively. Conclusions: D{sub max,V-1cm}3 is predictive for radiation-induced TLR. The tolerance doses obtained seem to be consistent with published data for highly conformal photon and proton irradiations. We could not detect any clinically relevant deviations between clinical findings and expectations based on predictions of the LEM.« less

A phase I study of gefitinib with concurrent dose-escalated weekly docetaxel and conformal three-dimensional thoracic radiation followed by consolidative docetaxel and maintenance gefitinib for patients with stage III non-small cell lung cancer.

PubMed

Center, Brian; Petty, William Jeffrey; Ayala, Diandra; Hinson, William H; Lovato, James; Capellari, James; Oaks, Timothy; Miller, Antonius A; Blackstock, Arthur William

2010-01-01

Concurrent radiation and chemotherapy is the standard of care for good performance status patients with stage III non-small cell lung cancer. Locoregional control remains a significant factor relating to poor outcome. Preclinical and early clinical data suggest that docetaxel and gefitinib have radiosensitizing activity. This study sought to define the maximum tolerated dose of weekly docetaxel that could be given with daily gefitinib and concurrent thoracic radiation therapy. Patients with histologically confirmed, inoperable stage III non-small cell lung cancer and good performance status (Eastern Cooperative Oncology Group 0-1) were eligible for this study. Patients received three-dimensional conformal thoracic radiation to a dose of 70 Gy concurrently with oral gefitinib at a dose of 250 mg daily and intravenous, weekly docetaxel at escalating doses from 15 to 30 mg/m2 in cohorts of patients. Patients were given a 2-week rest period after the concurrent therapy, during which they received only gefitinib. After the 2-week rest period, patients received consolidation chemotherapy with docetaxel 75 mg/m2 given every 21 days for two cycles. Maintenance gefitinib was continued until disease progression or study completion. Sixteen patients were enrolled on the study between December 2003 and April 2007 with the following characteristics: median age, 64 years (range 43-79 years); M/F: 9/7; and performance status 0/1, 1/15. Dose-limiting pulmonary toxicity and esophagitis were encountered at a weekly docetaxel dose of 25 mg/m2, resulting in a maximum tolerated dose of 20 mg/m2/wk. Overall, grade 3/4 hematologic toxicity was observed in 27% of patients. Grade 3/4 esophageal and pulmonary toxicities were reported in 27% and 20% of patients, respectively. The overall response rate was 46%, and the median survival for all patients was 21 months. Concurrent thoracic radiation with weekly docetaxel and daily gefitinib is feasible but results in moderate toxicity. For further studies, the recommended weekly docetaxel dose for this chemoradiation regimen is 20 mg/m2.

The dose-effect relationship of baclofen in alcohol dependence: A 1-year cohort study.

PubMed

Pignon, Baptiste; Labreuche, Julien; Auffret, Marine; Gautier, Sophie; Deheul, Sylvie; Simioni, Nicolas; Cottencin, Olivier; Bordet, Régis; Duhamel, Alain; Rolland, Benjamin

2017-07-01

Our aim is to study the relationship between dose of baclofen and effectiveness in alcohol dependence. Two hundred two patients with alcohol dependence, who received baclofen treatment for drinking reduction, were followed up for 1 year. For each patient-month of treatment, the maximum daily dose of baclofen (DDB) and average weekly alcohol consumption (AWAC) were calculated. We defined a favorable drinking outcome as an AWAC under 200 g/w for at least 2 consecutive months. We divided the DDB of each patient-month into 3 categories (low dose: <90 mg/d, medium dose: 90-150 mg/d, and high dose: >150 mg/d) and investigated the relationship between reaching a favorable outcome and the concurrent DDB category in a time-varying Cox regression analysis. Hazard ratios (HRs) were adjusted based on age, sex, and initial AWAC. One hundred forty subjects were followed during at least 1 month. Of these patients, 58 (41%) had a favorable drinking outcome. In comparison to low dose, medium dose was associated with a decreased rate of favorable drinking outcome (HR = 0.42; 95% CI [0.20, 0.88]), whereas no difference was found with high dose (HR = 1.31; 95% CI [0.65, 2.64]). The relationship between dose of baclofen and favorable drinking outcome was U-shaped, that is, was increased at low and high doses compared to medium doses. Copyright © 2017 John Wiley & Sons, Ltd.

Meta-analysis for deriving age- and gender-specific dose-response relationships between urinary cadmium concentration and {beta} {sub 2}-microglobulinuria under environmental exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gamo, Masashi; Ono, Kyoko; Nakanishi, Junko

2006-05-15

A meta-analysis was conducted to derive age- and gender-specific dose-response relationships between urinary cadmium (Cd) concentration and {beta} {sub 2}-microglobulinuria ({beta}2MG-uria) under environmental exposure. {beta}2MG-uria was defined by a cutoff point of 1000 {mu}g {beta} {sub 2}-microglobulin/g creatinine. We proposed a model for describing the relationships among the interindividual variabilities in urinary Cd concentration, the ratio of Cd concentrations in the target organ and in urine, and the threshold Cd concentration in the target organ. The parameters in the model were determined so that good agreement might be achieved between the prevalence rates of {beta}2MG-uria reported in the literature andmore » those estimated by the model. In this analysis, only the data from the literature on populations environmentally exposed to Cd were used. Using the model and estimated parameters, the prevalence rate of {beta}2MG-uria can be estimated for an age- and gender-specific subpopulation for which the distribution of urinary Cd concentrations is known. The maximum permissible level of urinary Cd concentration was defined as the maximum geometric mean of the urinary Cd concentration in an age- and gender-specific subpopulation that would not result in a statistically significant increase in the prevalence rate of {beta}2MG-uria. This was estimated to be approximately 3 {mu}g/g creatinine for a population in a small geographical area and approximately 2 {mu}g/g creatinine for a nationwide population.« less

Analgesia (mis)usage on a dental emergency service: a patient survey.

PubMed

Hommez, Geert; Ongena, B; Cauwels, R G E C; De Paepe, P; Christiaens, V; Jacquet, W

2018-04-01

Analgesics are one of the most frequently used medicines. Self-medication and misuse have been described in the literature. The purpose of this study was to document analgesic (mis)use in a population seeking emergency dental treatment. Patients consulting a dental emergency service were randomly asked to complete a questionnaire on analgesic use, knowledge and information on the analgesics and on their pain history. A photobook was used as an aid to identify products used. Descriptive statistics were combined with chi-square and Mann-Whitney U testing. Ninety-eight patients were included. Acetaminophen (69.4%) and ibuprofen (65.3%) were the most frequently used products. Nearly half of the subjects (43.9%) combined at least two analgesics. Although 42.9% of subjects were aware of the maximum daily dose, 62.2% of the subjects exceeded this limit, specifically 76.6% of subjects using ibuprofen and 32.4% of subjects using acetaminophen overdosing. Females overdosed significantly more than males. Ingestion on medical advice did not affect the overdose rates significantly. No significant relation was found between the absence of knowledge on the maximum daily dose and actual overdosing. No higher pain reduction was found in patients overdosing analgesics. The average number of days patients experienced pain before consulting the emergency unit was 12. A significant relation was found between the lag time and overdosing. A large portion of the patients overdosed analgesics. Even prior medical advice did not reduce significantly overdose rates. Dentists treating emergency cases clearly need to be aware of the high risk and high rates of overdosing analgesics in their patients.

Safety and tolerability of the first-in-class agent CPI-613 in combination with modified FOLFIRINOX in patients with metastatic pancreatic cancer: a single-centre, open-label, dose-escalation, phase 1 trial.

PubMed

Alistar, Angela; Morris, Bonny B; Desnoyer, Rodwige; Klepin, Heidi D; Hosseinzadeh, Keyanoosh; Clark, Clancy; Cameron, Amy; Leyendecker, John; D'Agostino, Ralph; Topaloglu, Umit; Boteju, Lakmal W; Boteju, Asela R; Shorr, Rob; Zachar, Zuzana; Bingham, Paul M; Ahmed, Tamjeed; Crane, Sandrine; Shah, Riddhishkumar; Migliano, John J; Pardee, Timothy S; Miller, Lance; Hawkins, Gregory; Jin, Guangxu; Zhang, Wei; Pasche, Boris

2017-06-01

Pancreatic cancer statistics are dismal, with a 5-year survival of less than 10%, and more than 50% of patients presenting with metastatic disease. Metabolic reprogramming is an emerging hallmark of pancreatic adenocarcinoma. CPI-613 is a novel anticancer agent that selectively targets the altered form of mitochondrial energy metabolism in tumour cells, causing changes in mitochondrial enzyme activities and redox status that lead to apoptosis, necrosis, and autophagy of tumour cells. We aimed to establish the maximum tolerated dose of CPI-613 when used in combination with modified FOLFIRINOX chemotherapy (comprising oxaliplatin, leucovorin, irinotecan, and fluorouracil) in patients with metastatic pancreatic cancer. In this single-centre, open-label, dose-escalation phase 1 trial, we recruited adult patients (aged ≥18 years) with newly diagnosed metastatic pancreatic adenocarcinoma from the Comprehensive Cancer Center of Wake Forest Baptist Medical Center (Winston-Salem, NC, USA). Patients had good bone marrow, liver and kidney function, and good performance status (Eastern Cooperative Oncology Group [ECOG] performance status 0-1). We studied CPI-613 in combination with modified FOLFIRINOX (oxaliplatin at 65 mg/m 2 , leucovorin at 400 mg/m 2 , irinotecan at 140 mg/m 2 , and fluorouracil 400 mg/m 2 bolus followed by 2400 mg/m 2 over 46 h). We applied a two-stage dose-escalation scheme (single patient and traditional 3+3 design). In the single-patient stage, one patient was accrued per dose level. The starting dose of CPI-613 was 500 mg/m 2 per day; the dose level was then escalated by doubling the previous dose if there were no adverse events worse than grade 2 within 4 weeks attributed as probably or definitely related to CPI-613. The traditional 3+3 dose-escalation stage was triggered if toxic effects attributed as probably or definitely related to CPI-613 were grade 2 or worse. The dose level for CPI-613 for the first cohort in the traditional dose-escalation stage was the same as that used in the last cohort of the single-patient dose-escalation stage. The primary objective was to establish the maximum tolerated dose of CPI-613 (as assessed by dose-limiting toxicities). This trial is registered with ClinicalTrials.gov, number NCT01835041, and is closed to recruitment. Between April 22, 2013, and Jan 8, 2016, we enrolled 20 patients. The maximum tolerated dose of CPI-613 was 500 mg/m 2 . The median number of treatment cycles given at the maximum tolerated dose was 11 (IQR 4-19). Median follow-up of the 18 patients treated at the maximum tolerated dose was 378 days (IQR 250-602). Two patients enrolled at a higher dose of 1000 mg/m 2 , and both had a dose-limiting toxicity. Two unexpected serious adverse events occurred, both for the first patient enrolled. Expected serious adverse events were: thrombocytopenia, anaemia, and lymphopenia (all for patient number 2; anaemia and lymphopenia were dose-limiting toxicities); hyperglycaemia (in patient number 7); hypokalaemia, hypoalbuminaemia, and sepsis (patient number 11); and neutropenia (patient number 20). No deaths due to adverse events were reported. For the 18 patients given the maximum tolerated dose, the most common grade 3-4 non-haematological adverse events were hyperglycaemia (ten [55%] patients), hypokalaemia (six [33%]), peripheral sensory neuropathy (five [28%]), diarrhoea (five [28%]), and abdominal pain (four [22%]). The most common grade 3-4 haematological adverse events were neutropenia (five [28%] of 18 patients), lymphopenia (five [28%]), anaemia (four [22%], and thrombocytopenia in three [17%]). Sensory neuropathy (all grade 1-3) was recorded in 17 (94%) of the 18 patients and was managed with dose de-escalation or discontinuation per standard of care. No patients died while on active treatment; 11 study participants died, with cause of death as terminal pancreatic cancer. Of the 18 patients given the maximum tolerated dose, 11 (61%) achieved an objective (complete or partial) response. A maximum tolerated dose of CPI-613 was established at 500 mg/m 2 when used in combination with modified FOLFIRINOX in patients with metastatic pancreatic cancer. The findings of clinical activity will require validation in a phase 2 trial. Comprehensive Cancer Center of Wake Forest Baptist Medical Center. Copyright © 2017 Elsevier Ltd. All rights reserved.

Investigation of intracranial peripheral dose arising from the treatment of large lesions with Leksell GammaKnife Perfexion.

PubMed

Ruschin, Mark; Nordström, Håkan; Kjäll, Per; Cho, Young-Bin; Jaffray, David

2009-06-01

This investigation involves quantifying the extent of intracranial peripheral dose arising from simulated targets situated in the skull-base or upper-spine region using the Leksell GammaKnife Perfexion treatment unit. For each of three spherical target volumes--denoted as Vs (4 cm3), VM (18 cm3), and VL (60 cm3)--three treatment plans were manually generated, one for each of the three collimator sizes--4, 8, and 16 mm. Each of the plans was delivered to a spherical dosimetry phantom with an insert containing EBT Gafchromic film. The total dose at 70 mm from the targets' edges, %D(70 mm), was measured as a function of elevation angle and expressed as a percentage of the prescription dose. The film insert was placed centered in the median sagittal plane (Leksell X = 100) and %D(70 mm) was measured for the angular range from 0 degree (superior/along Z axis) to 90 degrees (anterior/along Y axis). For a given collimator i, the irradiation time ti to treat a spherical target of volume V using the 50% isodose line was observed to follow a power-law relationship of the form ti = Ai(V/ Vi)n where Ai was the maximum dose divided by collimator dose rate and Vi was the volume encompassed by the 50% isodose line for a single shot. The mean value of n was 0.61 (range: 0.61-0.62). Along the superior (Z) direction (angle=0 degree) and up to angles of around 30 degrees, the %D(70 mm) was always highest for the 4 mm plans, followed by the 8 mm, followed by the 16 mm. In this angular range, the maximum measured %D(70 mm) was 1.7% of the prescription dose. The intracranial peripheral dose along the superior direction (combined scatter and leakage dose) resulting from irradiation of upper-spine or base-of-skull lesions is measured to be less than 2% of the prescription dose, even for very large (60 cm3) targets. The results of this study indicate that, for a given target volume, treatment plans consisting of only 4 mm shots yield larger peripheral dose in the superior direction than 8 mm shot only plans, which in turn yield larger peripheral dose than 16 mm shot only plans.

Dosimetric intercomparison of permanent Ho-166 seed's implants and HDR Ir-192 brachytherapy in breast cancer.

PubMed

de Campos, Tarcisio Passos Ribeiro; Nogueira, Luciana Batista; Trindade, Bruno; Cuperschmid, Ethel Mizrahy

2016-01-01

To provide a comparative dosimetric analysis of permanent implants of Ho(166)-seeds and temporary HDR Ir(192)-brachytherapy through computational simulation. Brachytherapy with Ir(192)-HDR or LDR based on temporary wires or permanent radioactive seed implants can be used as dose reinforcement for breast radiation therapy. Permanent breast implants have not been a practical clinical routine; although, I(125) and Pd(103)-seeds have already been reported. Biodegradable Ho(166)-ceramic-seeds have been addressed recently. Simulations of implants of nine Ho(166)-seeds and equivalent with HDR Ir(192)-brachytherapy were elaborated in MCNP5, shaped in a computational multivoxel simulator which reproduced a female thorax phantom. Spatial dose rate distributions and dose-volume histograms were generated. Protocol's analysis involving exposure time, seed's activities and dose were performed. Permanent Ho(166)-seed implants presented a maximum dose rate per unit of contained activity (MDR) of 1.1601 μGy h(-1) Bq(-1); and, a normalized MDR in standard points (8 mm, equidistant to 03-seeds - SP1, 10 mm - SP2) of 1.0% (SP1) and 0.5% (SP2), respectively. Ir(192)-brachytherapy presented MDR of 4.3945 × 10(-3) μGy h(-1) Bq(-1); and, 30% (SP1), and 20% (SP2). Therefore, seed's implant activities of 333 MBq (Ho(166)) and 259 GBq (Ir(192)) produced prescribed doses of 58 Gy (SP1; 5d) and 56 Gy (SP1, 5 fractions, 6 min), respectively. Breast Ho(166)-implants of 37-111 MBq are attractive due to the high dose rate near 6-10 mm from seeds, equivalent to Ir(192)-brachytherapy of 259 GBq (3 fractions, 6 min) providing similar dose in standard points at a week; however, with spatial dose distribution better confined. The seed positioning can be adjusted for controlling the breast tumor, in stages I and II, in flat and deep tumors, without any breast volumetric limitation.

Dosimetric Evaluation Between Megavoltage Cone-Beam Computed Tomography and Body Mass Index for Intracranial, Thoracic, and Pelvic Localization

DOE Office of Scientific and Technical Information (OSTI.GOV)

VanAntwerp, April E.; Raymond, Sarah M., E-mail: raymons9@ccf.org; Addington, Mark C.

2011-10-01

The aim of this study was to evaluate radiation dose for organs at risk (OAR) within the cranium, thorax, and pelvis from megavoltage cone-beam computed tomography (MV-CBCT). Using a clinical treatment planning system, CBCT doses were calculated from 60 patient datasets using 27.4 x 27.4 cm{sup 2} field size and 200{sup o} arc length. The body mass indices (BMIs) for these patients range from 17.2-48.4 kg/m{sup 2}. A total of 60 CBCT plans were created and calculated with heterogeneity corrections, with monitor units (MU) that varied from 8, 4, and 2 MU per plan. The isocenters of these plans weremore » placed at defined anatomical structures. The maximum dose, dose to the isocenter, and mean dose to the selected critical organs were analyzed. The study found that maximum and isocenter doses were weakly associated with BMI, but linearly associated with the total MU. Average maximum/isocenter doses in the cranium were 10.0 ({+-} 0.18)/7.0 ({+-} 0.08) cGy, 5.0 ({+-} 0.09)/3.5 ({+-} 0.05) cGy, and 2.5 ({+-} .04)/1.8 ({+-} 0.05) cGy for 8, 4, and 2 MU, respectively. Similar trends but slightly larger maximum/isocenter doses were found in the thoracic and pelvic regions. For the cranial region, the average mean doses with a total of 8 MU to the eye, lens, and brain were 9.7 ({+-} 0.12) cGy, 9.1 ({+-} 0.16) cGy, and 7.2 ({+-} 0.10) cGy, respectively. For the thoracic region, the average mean doses to the lung, heart, and spinal cord were 6.6 ({+-} 0.05) cGy, 6.9 ({+-} 1.2) cGy, and 4.7 ({+-} 0.8) cGy, respectively. For the pelvic region, the average mean dose to the femoral heads was 6.4 ({+-} 1.1) cGy. The MV-CBCT doses were linearly associated with the total MU but weakly dependent on patients' BMIs. Daily MV-CBCT has a cumulative effect on the total body dose and critical organs, which should be carefully considered for clinical impacts.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pokhrel, D; Sood, S; Badkul, R

Purpose: To evaluate XVMC computed rib doses for peripherally located non-small-cell-lung tumors treated with SBRT following RTOG-0915 guidelines. Methods: Twenty patients with solitary peripherally located non-small-cell-lung tumors were treated using XVMC-based SBRT to 50–54Gy in 5−3 fractions, respectively, for PTV(V100%)=95%. Based on 4D-CT, ITV was delineated on MaximumIP images and organs-at-risk(OARs) including ribs were contoured on MeanIP images. Mean PTV(ITV+5mm uniform margin) was 46.1±38.7cc (range, 11.1–163.0cc). XVMC SBRT treatment plans were generated with a combination of non-coplanar 3D-conformal arcs/beams, and were delivered by Novalis-TX consisting of HD-MLCs and a 6MV-SRS(1000MU/min) beam, following RTOG-0915 criteria. XVMC rib maximum dose and dosemore » to <1cc, <5cc, <10cc were evaluated as a function of PTV, prescription dose and 3D-distance from tumor isocenter to the most proximal rib contour. Plans were re-computed using heterogeneity-corrected pencil-beam (PB-hete) algorithm utilizing identical beam geometry/MLC positions and MUs and subsequently compared to XVMC. Results: XVMC average maximum rib dose was 50.9±6.4Gy (range, 35.1–59.3Gy). XVMC mean rib dose to <1cc was 41.6±5.6Gy (range, 27.9–47.9Gy), <5cc was 31.2±7.3Gy (range, 10.6–43.1Gy), and <10cc was 21.2±8.7Gy (range, 1.1–36Gy), respectively. For the given prescription, correlation between PTV and rib doses to <5cc (p=0.005) and <10cc (p=0.018) was observed. 3D-distance from the tumor isocenter to the proximal rib contour strongly correlated with maximum rib dose (p=0.0001). PB-hete algorithm overestimated maximum rib dose and dose to <1cc, <5cc, and <10cc of ribs by 5%, 3%, 3%, and 3%, respectively. Conclusion: PB-hete overestimates ribs dose relative to XVMC. Since all the clinical XVMC plans were generated without compromising the target coverage (per RTOG-0915), almost all patient’s ribs doses were higher than the protocol guidelines. As expected, larger tumor size and proximity to ribs received higher absolute dose to ribs. Prospective observation is needed to determine if XVMC delivered rib doses correlates with patient symptoms including chest wall pain and/or rib fractures.« less

Emergency department patient knowledge concerning acetaminophen (paracetamol) in over-the-counter and prescription analgesics.

PubMed

Fosnocht, D; Taylor, J R; Caravati, E M

2008-04-01

This study was designed to evaluate patient knowledge of the acetaminophen (paracetamol) content of commonly used pain medications and the maximum daily recommended dose of acetaminophen. A prospective, convenience sample of emergency department patients were enrolled. Data were recorded using a standardised questionnaire over 4 months. 1009 patients were enrolled. 492 patients (49%) did not know if Tylenol contained acetaminophen (paracetamol). The majority (66-90%) of patients did not know if Lortab, Vicodin, Percocet, non-aspirin pain reliever, ibuprofen, Motrin, or Advil contained acetaminophen. 568 patients (56%) reported not knowing the maximum daily dose of acetaminophen and only 71 patients (7%) reported the correct daily dose. Patient knowledge of the acetaminophen content of commonly used analgesic medications and its maximum recommended daily dose is limited. This may contribute to unintentional repeated supratherapeutic ingestion (RSTI) of acetaminophen, or overdose.

Reconstruction of Absorbed Doses to Fibroglandular Tissue of the Breast of Women undergoing Mammography (1960 to the Present)

PubMed Central

Thierry-Chef, Isabelle; Simon, Steven L.; Weinstock, Robert M.; Kwon, Deukwoo; Linet, Martha S.

2013-01-01

The assessment of potential benefits versus harms from mammographic examinations as described in the controversial breast cancer screening recommendations of the U.S. Preventive Task Force included limited consideration of absorbed dose to the fibroglandular tissue of the breast (glandular tissue dose), the tissue at risk for breast cancer. Epidemiological studies on cancer risks associated with diagnostic radiological examinations often lack accurate information on glandular tissue dose, and there is a clear need for better estimates of these doses. Our objective was to develop a quantitative summary of glandular tissue doses from mammography by considering sources of variation over time in key parameters including imaging protocols, x-ray target materials, voltage, filtration, incident air kerma, compressed breast thickness, and breast composition. We estimated the minimum, maximum, and mean values for glandular tissue dose for populations of exposed women within 5-year periods from 1960 to the present, with the minimum to maximum range likely including 90% to 95% of the entirety of the dose range from mammography in North America and Europe. Glandular tissue dose from a single view in mammography is presently about 2 mGy, about one-sixth the dose in the 1960s. The ratio of our estimates of maximum to minimum glandular tissue doses for average-size breasts was about 100 in the 1960s compared to a ratio of about 5 in recent years. Findings from our analysis provide quantitative information on glandular tissue doses from mammographic examinations which can be used in epidemiologic studies of breast cancer. PMID:21988547

Dosimetric verification of IMRT treatment planning using Monte Carlo simulations for prostate cancer

NASA Astrophysics Data System (ADS)

Yang, J.; Li, J.; Chen, L.; Price, R.; McNeeley, S.; Qin, L.; Wang, L.; Xiong, W.; Ma, C.-M.

2005-03-01

The purpose of this work is to investigate the accuracy of dose calculation of a commercial treatment planning system (Corvus, Normos Corp., Sewickley, PA). In this study, 30 prostate intensity-modulated radiotherapy (IMRT) treatment plans from the commercial treatment planning system were recalculated using the Monte Carlo method. Dose-volume histograms and isodose distributions were compared. Other quantities such as minimum dose to the target (Dmin), the dose received by 98% of the target volume (D98), dose at the isocentre (Diso), mean target dose (Dmean) and the maximum critical structure dose (Dmax) were also evaluated based on our clinical criteria. For coplanar plans, the dose differences between Monte Carlo and the commercial treatment planning system with and without heterogeneity correction were not significant. The differences in the isocentre dose between the commercial treatment planning system and Monte Carlo simulations were less than 3% for all coplanar cases. The differences on D98 were less than 2% on average. The differences in the mean dose to the target between the commercial system and Monte Carlo results were within 3%. The differences in the maximum bladder dose were within 3% for most cases. The maximum dose differences for the rectum were less than 4% for all the cases. For non-coplanar plans, the difference in the minimum target dose between the treatment planning system and Monte Carlo calculations was up to 9% if the heterogeneity correction was not applied in Corvus. This was caused by the excessive attenuation of the non-coplanar beams by the femurs. When the heterogeneity correction was applied in Corvus, the differences were reduced significantly. These results suggest that heterogeneity correction should be used in dose calculation for prostate cancer with non-coplanar beam arrangements.

Effect of gamma radiation on native endolithic microorganisms from a radioactive waste deposit site.

PubMed

Pitonzo, B J; Amy, P S; Rudin, M

1999-07-01

A time-course experiment was conducted to evaluate the effects of gamma radiation on the indigenous microbiota present in rock obtained from Yucca Mountain, Nevada Test Site. Microcosms were constructed by placing pulverized Yucca Mountain rock in polystyrene cylinders. Continuous exposure (96 h) at a dose rate of 1.63 Gy/min was used to mimic the near-field environment surrounding waste canisters. The expected maximum surface dose rate from one unbreached canister designed to contain spent nuclear fuels is 0.06 Gy/min. Considering the current repository packing design, multiple canisters within one vault, the cumulative dose rate may well approach that used in this experiment. The microbial communities were characterized after receiving cumulative doses of 0, 0.098, 0. 58, 2.33, 4.67, 7.01 and 9.34 kGy. Radiation-resistant microorganisms in the pulverized rock became viable but nonculturable (VBNC) after a cumulative dose of 2.33 kGy. VBNC microorganisms lose the ability to grow on media on which they have routinely been cultured in response to the environmental stress imposed (i.e. radiation) but can be detected throughout the time course using direct fluorescence microscopy techniques. Two representative exopolysaccharide-producing isolates from Yucca Mountain were exposed to the same radiation regimen in sand microcosms. One isolate was much more radiation-resistant than the other, but both had greater resistance than the general microbial community based on culturable counts. However, when respiring cell counts (VBNC) were compared after irradiation, the results would indicate much more radiation resistance of the individual isolates and the microbial community in general. These results have significant implications for underground storage of nuclear waste as they indicate that indigenous microorganisms are capable of surviving gamma irradiation in a VBNC state.

Bolus-dependent dosimetric effect of positioning errors for tangential scalp radiotherapy with helical tomotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lobb, Eric, E-mail: eclobb2@gmail.com

2014-04-01

The dosimetric effect of errors in patient position is studied on-phantom as a function of simulated bolus thickness to assess the need for bolus utilization in scalp radiotherapy with tomotherapy. A treatment plan is generated on a cylindrical phantom, mimicking a radiotherapy technique for the scalp utilizing primarily tangential beamlets. A planning target volume with embedded scalplike clinical target volumes (CTVs) is planned to a uniform dose of 200 cGy. Translational errors in phantom position are introduced in 1-mm increments and dose is recomputed from the original sinogram. For each error the maximum dose, minimum dose, clinical target dose homogeneitymore » index (HI), and dose-volume histogram (DVH) are presented for simulated bolus thicknesses from 0 to 10 mm. Baseline HI values for all bolus thicknesses were in the 5.5 to 7.0 range, increasing to a maximum of 18.0 to 30.5 for the largest positioning errors when 0 to 2 mm of bolus is used. Utilizing 5 mm of bolus resulted in a maximum HI value of 9.5 for the largest positioning errors. Using 0 to 2 mm of bolus resulted in minimum and maximum dose values of 85% to 94% and 118% to 125% of the prescription dose, respectively. When using 5 mm of bolus these values were 98.5% and 109.5%. DVHs showed minimal changes in CTV dose coverage when using 5 mm of bolus, even for the largest positioning errors. CTV dose homogeneity becomes increasingly sensitive to errors in patient position as bolus thickness decreases when treating the scalp with primarily tangential beamlets. Performing a radial expansion of the scalp CTV into 5 mm of bolus material minimizes dosimetric sensitivity to errors in patient position as large as 5 mm and is therefore recommended.« less

Impact of head and neck cancer adaptive radiotherapy to spare the parotid glands and decrease the risk of xerostomia.

PubMed

Castelli, Joel; Simon, Antoine; Louvel, Guillaume; Henry, Olivier; Chajon, Enrique; Nassef, Mohamed; Haigron, Pascal; Cazoulat, Guillaume; Ospina, Juan David; Jegoux, Franck; Benezery, Karen; de Crevoisier, Renaud

2015-01-09

Large anatomical variations occur during the course of intensity-modulated radiation therapy (IMRT) for locally advanced head and neck cancer (LAHNC). The risks are therefore a parotid glands (PG) overdose and a xerostomia increase. The purposes of the study were to estimate: - the PG overdose and the xerostomia risk increase during a "standard" IMRT (IMRTstd); - the benefits of an adaptive IMRT (ART) with weekly replanning to spare the PGs and limit the risk of xerostomia. Fifteen patients received radical IMRT (70 Gy) for LAHNC. Weekly CTs were used to estimate the dose distributions delivered during the treatment, corresponding either to the initial planning (IMRTstd) or to weekly replanning (ART). PGs dose were recalculated at the fraction, from the weekly CTs. PG cumulated doses were then estimated using deformable image registration. The following PG doses were compared: pre-treatment planned dose, per-treatment IMRTstd and ART. The corresponding estimated risks of xerostomia were also compared. Correlations between anatomical markers and dose differences were searched. Compared to the initial planning, a PG overdose was observed during IMRTstd for 59% of the PGs, with an average increase of 3.7 Gy (10.0 Gy maximum) for the mean dose, and of 8.2% (23.9% maximum) for the risk of xerostomia. Compared to the initial planning, weekly replanning reduced the PG mean dose for all the patients (p<0.05). In the overirradiated PG group, weekly replanning reduced the mean dose by 5.1 Gy (12.2 Gy maximum) and the absolute risk of xerostomia by 11% (p<0.01) (30% maximum). The PG overdose and the dosimetric benefit of replanning increased with the tumor shrinkage and the neck thickness reduction (p<0.001). During the course of LAHNC IMRT, around 60% of the PGs are overdosed of 4 Gy. Weekly replanning decreased the PG mean dose by 5 Gy, and therefore by 11% the xerostomia risk.

Characteristic performance evaluation of a photon counting Si strip detector for low dose spectral breast CT imaging

PubMed Central

Cho, Hyo-Min; Barber, William C.; Ding, Huanjun; Iwanczyk, Jan S.; Molloi, Sabee

2014-01-01

Purpose: The possible clinical applications which can be performed using a newly developed detector depend on the detector's characteristic performance in a number of metrics including the dynamic range, resolution, uniformity, and stability. The authors have evaluated a prototype energy resolved fast photon counting x-ray detector based on a silicon (Si) strip sensor used in an edge-on geometry with an application specific integrated circuit to record the number of x-rays and their energies at high flux and fast frame rates. The investigated detector was integrated with a dedicated breast spectral computed tomography (CT) system to make use of the detector's high spatial and energy resolution and low noise performance under conditions suitable for clinical breast imaging. The aim of this article is to investigate the intrinsic characteristics of the detector, in terms of maximum output count rate, spatial and energy resolution, and noise performance of the imaging system. Methods: The maximum output count rate was obtained with a 50 W x-ray tube with a maximum continuous output of 50 kVp at 1.0 mA. A109Cd source, with a characteristic x-ray peak at 22 keV from Ag, was used to measure the energy resolution of the detector. The axial plane modulation transfer function (MTF) was measured using a 67 μm diameter tungsten wire. The two-dimensional (2D) noise power spectrum (NPS) was measured using flat field images and noise equivalent quanta (NEQ) were calculated using the MTF and NPS results. The image quality parameters were studied as a function of various radiation doses and reconstruction filters. The one-dimensional (1D) NPS was used to investigate the effect of electronic noise elimination by varying the minimum energy threshold. Results: A maximum output count rate of 100 million counts per second per square millimeter (cps/mm2) has been obtained (1 million cps per 100 × 100 μm pixel). The electrical noise floor was less than 4 keV. The energy resolution measured with the 22 keV photons from a 109Cd source was less than 9%. A reduction of image noise was shown in all the spatial frequencies in 1D NPS as a result of the elimination of the electronic noise. The spatial resolution was measured just above 5 line pairs per mm (lp/mm) where 10% of MTF corresponded to 5.4 mm−1. The 2D NPS and NEQ shows a low noise floor and a linear dependence on dose. The reconstruction filter choice affected both of the MTF and NPS results, but had a weak effect on the NEQ. Conclusions: The prototype energy resolved photon counting Si strip detector can offer superior imaging performance for dedicated breast CT as compared to a conventional energy-integrating detector due to its high output count rate, high spatial and energy resolution, and low noise characteristics, which are essential characteristics for spectral breast CT imaging. PMID:25186390

Pharmacokinetics of tramadol after subcutaneous administration in a critically ill population and in a healthy cohort

PubMed Central

2014-01-01

Background Tramadol is an atypical centrally acting analgesic agent available as both oral and parenteral preparations. For patients who are unable to take tramadol orally, the subcutaneous route of administration offers an easy alternative to intravenous or intramuscular routes. This study aimed to characterise the absorption pharmacokinetics of a single subcutaneous dose of tramadol in severely ill patients and in healthy subjects. Methods/design Blood samples (5 ml) taken at intervals from 2 minutes to 24 hours after a subcutaneous dose of tramadol (50 mg) in 15 patients (13 male, two female) and eight healthy male subjects were assayed using high performance liquid chromatography. Pharmacokinetic parameters were derived using a non-compartmental approach. Results There were no statistically significant differences between the two groups in the following parameters (mean ± SD): maximum venous concentration 0.44 ± 0.18 (patients) vs. 0.47 ± 0.13 (healthy volunteers) mcg/ml (p = 0.67); area under the plasma concentration-time curve 177 ± 109 (patients) vs. 175 ± 75 (healthy volunteers) mcg/ml*min (p = 0.96); time to maximum venous concentration 23.3 ± 2 (patients) vs. 20.6 ± 18.8 (healthy volunteers) minutes (p = 0.73) and mean residence time 463 ± 233 (patients) vs. 466 ± 224 (healthy volunteers) minutes (p = 0.97). Conclusions The similar time to maximum venous concentration and mean residence time suggest similar absorption rates between the two groups. These results indicate that the same dosing regimens for subcutaneous tramadol administration may therefore be used in both healthy subjects and severely ill patients. Trial registration ACTRN12611001018909 PMID:24914400

Proposal for a New Prognostic Score for Linac-Based Radiosurgery in Cerebral Arteriovenous Malformations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Milker-Zabel, Stefanie, E-mail: Stefanie_Milker-Zabel@med.uni-heidelberg.de; Kopp-Schneider, Annette; Wiesbauer, Hannah

2012-06-01

Purpose: We evaluate patient-, angioma-, and treatment-specific factors for successful obliteration of cerebral arteriovenous malformations (AVM) to develop a new appropriate score to predict patient outcome after linac-based radiosurgery (RS). Methods and Materials: This analysis in based on 293 patients with cerebral AVM. Mean age at treatment was 38.8 years (4-73 years). AVM classification according Spetzler-Martin was 55 patients Grade I (20.5%), 114 Grade II (42.5%), 79 Grade III (29.5%), 19 Grade IV (7.1%), and 1 Grade V (0.4%). Median maximum AVM diameter was 3.0 cm (range, 0.3-10 cm). Median dose prescribed to the 80% isodose was 18 Gy (range,more » 12-22 Gy). Eighty-five patients (29.1%) had prior partial embolization; 141 patients (51.9%) experienced intracranial hemorrhage before RS. Median follow-up was 4.2 years. Results: Age at treatment, maximum diameter, nidus volume, and applied dose were significant factors for successful obliteration. Under presumption of proportional hazard in the dose range between 12 and 22 Gy/80% isodose, an increase of obliteration rate of approximately 25% per Gy was seen. On the basis of multivariate analysis, a prediction score was calculated including AVM maximum diameter and age at treatment. The prediction error up to the time point 8 years was 0.173 for the Heidelberg score compared with the Kaplan-Meier value of 0.192. An increase of the score of 1 point results in a decrease of obliteration chance by a factor of 0.447. Conclusion: The proposed score is linac-based radiosurgery-specific and easy to handle to predict patient outcome. Further validation on an independent patient cohort is necessary.« less

The features of radiation dose variations onboard ISS and Mir space station: comparative study.

PubMed

Tverskaya, L V; Panasyuk, M I; Reizman, S Ya; Sosnovets, E N; Teltsov, M V; Tsetlin, V V

2004-01-01

The dynamics of the ISS-measured radiation dose variations since August 2000 is studied. Use is made of the data obtained with the R-16 instrument, which consists of two ionization chambers behind different shielding thicknesses. The doses recorded during solar energetic particle (SEP) events are compared with the data obtained also by R-16 on Mir space station. The SEP events in the solar maximum of the current cycle make a much smaller contribution to the radiation dose compared with the October 1989 event recorded on Mir space station. In the latter event, the proton intensity was peaking during a strong magnetic storm. The storm-time effect of solar proton geomagnetic cutoff decreases on dose variations is estimated. The dose variations on Mir space stations due to formation of a new radiation belt of high-energy protons and electrons during a sudden commencement of March 24, 1991 storm are also studied. It was for the first time throughout the ISS and Mir dose measurement period that the counting rates recorded by both R-16 channels on ISS in 2001-2002 were nearly the same during some time intervals. This effect may arise from the decreases of relativistic electron fluxes in the outer radiation belt. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

Performance of toxicity probability interval based designs in contrast to the continual reassessment method

PubMed Central

Horton, Bethany Jablonski; Wages, Nolan A.; Conaway, Mark R.

2016-01-01

Toxicity probability interval designs have received increasing attention as a dose-finding method in recent years. In this study, we compared the two-stage, likelihood-based continual reassessment method (CRM), modified toxicity probability interval (mTPI), and the Bayesian optimal interval design (BOIN) in order to evaluate each method's performance in dose selection for Phase I trials. We use several summary measures to compare the performance of these methods, including percentage of correct selection (PCS) of the true maximum tolerable dose (MTD), allocation of patients to doses at and around the true MTD, and an accuracy index. This index is an efficiency measure that describes the entire distribution of MTD selection and patient allocation by taking into account the distance between the true probability of toxicity at each dose level and the target toxicity rate. The simulation study considered a broad range of toxicity curves and various sample sizes. When considering PCS, we found that CRM outperformed the two competing methods in most scenarios, followed by BOIN, then mTPI. We observed a similar trend when considering the accuracy index for dose allocation, where CRM most often outperformed both the mTPI and BOIN. These trends were more pronounced with increasing number of dose levels. PMID:27435150

InfuShield: a shielded enclosure for administering therapeutic radioisotope treatments using standard syringe pumps

PubMed Central

Pratt, Brenda E.; Chittenden, Sarah J.; Murray, Iain S.; Causer, Louise; Grey, Matthew J.; Gear, Jonathan I.; Du, Yong; Flux, Glenn D.

2017-01-01

The administration of radionuclide therapies presents significant radiation protection challenges. The aim of this work was to develop a delivery system for intravenous radioisotope therapies to substantially moderate radiation exposures to staff and operators. A novel device (InfuShield) was designed and tested before being used clinically. The device consists of a shielded enclosure which contains the therapeutic activity and, through the hydraulic action of back-to-back syringes, allows the activity to be administered using a syringe pump external to the enclosure. This enables full access to the pump controls while simultaneously reducing dose to the operator. The system is suitable for use with all commercially available syringe pumps and does not require specific consumables, maximising both the flexibility and economy of the system. Dose rate measurements showed that at key stages in an 131I mIBG treatment procedure, InfuShield can reduce dose to operators by several orders of magnitude. Tests using typical syringes and infusion speeds show no significant alteration in administered flow rates (maximum of 1.2%). The InfuShield system provides a simple, safe and low cost method of radioisotope administration. PMID:28187040

Guidelines for Posting Soil Contamination Areas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mcnaughton, Michael; Eisele, William

All soil guidelines were determined using RESRAD, version 6.1. All offsite guidelines are based on 15 mrem/year. This dose rate is sufficiently low to protect human health and is in accordance with DOE guidance and the proposed EPA 40-CFR-196 regulations for members of the public (never promulgated). For those onsite areas where general employees (non-radiological workers) could have routine access, soil concentrations should be based on a dose rate of 30 mrem/year (approximately one-third of the onsite LANL non-radiological worker dose of 100 mrem/year). In this case, soil concentration guidelines may be obtained by doubling the 15 mrem/year guidelines. Severalmore » scenarios were developed to provide maximum flexibility for application of the guidelines. The offsite guidelines were developed using: residential scenarios for both adults and children; a construction worker scenario; a resource user (e.g., a hunter) scenario; a child playing within canyon reaches scenario, a trail using jogger within canyon reaches scenario, and a trail using hiker within canyon reaches scenario. The residential guidelines represent the lowest values from both the adult residential scenario and the child residential scenario.« less

The small-molecule TNF-α inhibitor, UTL-5g, delays deaths and increases survival rates for mice treated with high doses of cisplatin

PubMed Central

Media, Joseph; Chen, Ben; Valeriote, Fredrick

2013-01-01

Purpose UTL-5g is a novel small-molecule chemoprotector that lowers hepatotoxicity, nephrotoxicity, and myelotoxicity induced by cisplatin through TNF-α inhibition among other factors. The objective of this study was to investigate whether UTL-5g can reduce the overall acute toxicity of cisplatin and increase cisplatin tolerability in mice. Materials and Methods BDF1 female mice were treated individually with UTL-5g (suspended in Ora-Plus) by oral gavage at 60 mg/kg, 30 min before i.p. injection of cisplatin at 10, 15, and 20 mg/kg respectively on Day 0. Starting from Day 1, individual mice were again treated daily by the same dose of UTL-5g for 4 consecutive days. Survivals and bodyweights were monitored. Results UTL-5g treatment increased the survival rate and delayed the time to death for mice treated with 150% of the maximum tolerated dose (MTD) of cisplatin (15 mg/kg). Likewise, at 200% of the MTD of cisplatin (20 mg/kg), treatment of UTL-5g increased the survival rate and delayed the time to death. Treatment of UTL-5g did not have a significant effect on weight-loss induced by cisplatin indicating that bodyweight may not be a sensitive enough measure for chemoprotection of UTL-5g against cisplatin. Conclusions In summary, UTL-5g delayed deaths and increased survival rates of mice treated by high doses of cisplatin indicating that UTL-5g is capable of reducing the overall acute toxicity of cisplatin and increased cisplatin tolerability in mice; this is in line with the specific chemoprotective effects of UTL-5g previously reported. Further investigation of UTL-5g in combination with cisplatin is warranted. PMID:23881213

The small-molecule TNF-α inhibitor, UTL-5g, delays deaths and increases survival rates for mice treated with high doses of cisplatin.

PubMed

Shaw, Jiajiu; Media, Joseph; Chen, Ben; Valeriote, Fredrick

2013-09-01

UTL-5g is a novel small-molecule chemoprotector that lowers hepatotoxicity, nephrotoxicity, and myelotoxicity induced by cisplatin through TNF-α inhibition among other factors. The objective of this study was to investigate whether UTL-5g can reduce the overall acute toxicity of cisplatin and increase cisplatin tolerability in mice. BDF1 female mice were treated individually with UTL-5g (suspended in Ora-Plus) by oral gavage at 60 mg/kg, 30 min before i.p. injection of cisplatin at 10, 15, and 20 mg/kg, respectively, on Day 0. Starting from Day 1, individual mice were again treated daily by the same dose of UTL-5g for 4 consecutive days. Survivals and body weights were monitored. UTL-5g treatment increased the survival rate and delayed the time to death for mice treated with 150 % of the maximum tolerated dose (MTD) of cisplatin (15 mg/kg). Likewise, at 200 % of the MTD of cisplatin (20 mg/kg), treatment of UTL-5g increased the survival rate and delayed the time to death. Treatment of UTL-5g did not have a significant effect on weight loss induced by cisplatin, indicating that body weight may not be a sensitive-enough measure for chemoprotection of UTL-5g against cisplatin. In summary, UTL-5g delayed deaths and increased survival rates of mice treated by high doses of cisplatin, indicating that UTL-5g is capable of reducing the overall acute toxicity of cisplatin and increased cisplatin tolerability in mice; this is in line with the specific chemoprotective effects of UTL-5g previously reported. Further investigation of UTL-5g in combination with cisplatin is warranted.

Intensity-modulated radiation therapy for pancreatic and prostate cancer using pulsed low–dose rate delivery techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Jie; Lang, Jinyi; Wang, Pei

2014-01-01

Reirradiation of patients who were previously treated with radiotherapy is vastly challenging. Pulsed low–dose rate (PLDR) external beam radiotherapy has the potential to reduce normal tissue toxicities while providing significant tumor control for recurrent cancers. This work investigates treatment planning techniques for intensity-modulated radiation therapy (IMRT)-based PLDR treatment of various sites, including cases with pancreatic and prostate cancer. A total of 20 patients with clinical recurrence were selected for this study, including 10 cases with pancreatic cancer and 10 with prostate cancer. Large variations in the target volume were included to test the ability of IMRT using the existing treatmentmore » planning system and optimization algorithm to deliver uniform doses in individual gantry angles/fields for PLDR treatments. Treatment plans were generated with 10 gantry angles using the step-and-shoot IMRT delivery technique, which can be delivered in 3-minute intervals to achieve an effective low dose rate of 6.7 cGy/min. Instead of dose constraints on critical structures, ring structures were mainly used in PLDR-IMRT optimization. In this study, the PLDR-IMRT plans were compared with the PLDR-3-dimensional conformal radiation therapy (3DCRT) plans and the PLDR-RapidArc plans. For the 10 cases with pancreatic cancer that were investigated, the mean planning target volume (PTV) dose for each gantry angle in the PLDR-IMRT plans ranged from 17.6 to 22.4 cGy. The maximum doses ranged between 22.9 and 34.8 cGy. The minimum doses ranged from 8.2 to 17.5 cGy. For the 10 cases with prostate cancer that were investigated, the mean PTV doses for individual gantry angles ranged from 18.8 to 22.6 cGy. The maximum doses per gantry angle were between 24.0 and 34.7 cGy. The minimum doses per gantry angle ranged from 4.4 to 17.4 cGy. A significant reduction in the organ at risk (OAR) dose was observed with the PLDR-IMRT plan when compared with that using the PLDR-3DCRT plan. The volume receiving an 18-Gy (V{sub 18}) dose for the left and right kidneys was reduced by 10.6% and 12.5%, respectively, for the pancreatic plans. The volume receiving a 45-Gy (V{sub 45}) dose for the small bowel decreased from 65.3% to 45.5%. For the cases with prostate cancer, the volume receiving a 40-Gy (V{sub 40}) dose for the bladder and the rectum was reduced significantly by 25.1% and 51.2%, respectively. When compared with the RapidArc technique, the volume receiving a 30-Gy (V{sub 30}) dose for the left and the right kidneys was lower in the IMRT plans. For most OARs, no significant differences were observed between the PLDR-IMRT and the PLDR-RapidArc plans. These results clearly demonstrated that the PLDR-IMRT plan was suitable for PLDR pancreatic and prostate cancer treatments in terms of the overall plan quality. A significant reduction in the OAR dose was achieved with the PLDR-IMRT plan when compared with that using the PLDR-3DCRT plan. For most OARs, no significant differences were observed between the PLDR-IMRT and the PLDR-RapidArc plans. When compared with the PLDR-3DCRT plan, the PLDR-IMRT plan could provide superior target coverage and normal tissue sparing for PLDR reirradiation of recurrent pancreatic and prostate cancers. The PLDR-IMRT plan is an effective treatment choice for recurrent cancers in most cancer centers.« less

Fine and ultrafine particle doses in the respiratory tract from digital printing operations.

PubMed

Voliotis, Aristeidis; Karali, Irene; Kouras, Athanasios; Samara, Constantini

2017-01-01

In this study, we report for the first time particle number doses in different parts of the human respiratory tract and real-time deposition rates for particles in the 10 nm to 10 μm size range emitted by digital printing operations. Particle number concentrations (PNCs) and size distribution were measured in a typical small-sized printing house using a NanoScan scanning mobility particle sizer and an optical particle sizer. Particle doses in human lung were estimated applying a multiple-path particle dosimetry model under two different breathing scenarios. PNC was dominated by the ultrafine particle fractions (UFPs, i.e., particles smaller than 100 nm) exhibiting almost nine times higher levels in comparison to the background values. The average deposition rate fοr each scenario in the whole lung was estimated at 2.0 and 2.9 × 10 7 particles min -1 , while the respective highest particle dose in the tracheobronchial tree (2.0 and 2.9 × 10 9 particles) was found for diameter of 50 nm. The majority of particles appeared to deposit in the acinar region and most of them were in the UFP size range. For both scenarios, the maximum deposition density (9.5 × 10 7 and 1.5 × 10 8 particles cm -2 ) was observed at the lobar bronchi. Overall, the differences in the estimated particle doses between the two scenarios were 30-40% for both size ranges.

Case Example of Dose Optimization Using Data From Bortezomib Dose-Finding Clinical Trials

PubMed Central

Backenroth, Daniel; Cheung, Ying Kuen Ken; Hershman, Dawn L.; Vulih, Diana; Anderson, Barry; Ivy, Percy; Minasian, Lori

2016-01-01

Purpose The current dose-finding methodology for estimating the maximum tolerated dose of investigational anticancer agents is based on the cytotoxic chemotherapy paradigm. Molecularly targeted agents (MTAs) have different toxicity profiles, which may lead to more long-lasting mild or moderate toxicities as well as to late-onset and cumulative toxicities. Several approved MTAs have been poorly tolerated during long-term administration, leading to postmarketing dose optimization studies to re-evaluate the optimal treatment dose. Using data from completed bortezomib dose-finding trials, we explore its toxicity profile, optimize its dose, and examine the appropriateness of current designs for identifying an optimal dose. Patients and Methods We classified the toxicities captured from 481 patients in 14 bortezomib dose-finding studies conducted through the National Cancer Institute Cancer Therapy Evaluation Program, computed the incidence of late-onset toxicities, and compared the incidence of dose-limiting toxicities (DLTs) among groups of patients receiving different doses of bortezomib. Results A total of 13,008 toxicities were captured: 46% of patients’ first DLTs and 88% of dose reductions or discontinuations of treatment because of toxicity were observed after the first cycle. Moreover, for the approved dose of 1.3 mg/m2, the estimated cumulative incidence of DLT was > 50%, and the estimated cumulative incidence of dose reduction or treatment discontinuation because of toxicity was nearly 40%. Conclusions When considering the entire course of treatment, the approved bortezomib dose exceeds the conventional ceiling DLT rate of 20% to 33%. Retrospective analysis of trial data provides an opportunity for dose optimization of MTAs. Future dose-finding studies of MTAs should take into account late-onset toxicities to ensure that a tolerable dose is identified for future efficacy and comparative trials. PMID:26926682

Case Example of Dose Optimization Using Data From Bortezomib Dose-Finding Clinical Trials.

PubMed

Lee, Shing M; Backenroth, Daniel; Cheung, Ying Kuen Ken; Hershman, Dawn L; Vulih, Diana; Anderson, Barry; Ivy, Percy; Minasian, Lori

2016-04-20

The current dose-finding methodology for estimating the maximum tolerated dose of investigational anticancer agents is based on the cytotoxic chemotherapy paradigm. Molecularly targeted agents (MTAs) have different toxicity profiles, which may lead to more long-lasting mild or moderate toxicities as well as to late-onset and cumulative toxicities. Several approved MTAs have been poorly tolerated during long-term administration, leading to postmarketing dose optimization studies to re-evaluate the optimal treatment dose. Using data from completed bortezomib dose-finding trials, we explore its toxicity profile, optimize its dose, and examine the appropriateness of current designs for identifying an optimal dose. We classified the toxicities captured from 481 patients in 14 bortezomib dose-finding studies conducted through the National Cancer Institute Cancer Therapy Evaluation Program, computed the incidence of late-onset toxicities, and compared the incidence of dose-limiting toxicities (DLTs) among groups of patients receiving different doses of bortezomib. A total of 13,008 toxicities were captured: 46% of patients' first DLTs and 88% of dose reductions or discontinuations of treatment because of toxicity were observed after the first cycle. Moreover, for the approved dose of 1.3 mg/m(2), the estimated cumulative incidence of DLT was > 50%, and the estimated cumulative incidence of dose reduction or treatment discontinuation because of toxicity was nearly 40%. When considering the entire course of treatment, the approved bortezomib dose exceeds the conventional ceiling DLT rate of 20% to 33%. Retrospective analysis of trial data provides an opportunity for dose optimization of MTAs. Future dose-finding studies of MTAs should take into account late-onset toxicities to ensure that a tolerable dose is identified for future efficacy and comparative trials. © 2016 by American Society of Clinical Oncology.

Induction of labor using prostaglandin E2 (PGE2) vaginal gel in triacetin base. An efficacy study comparing two dosage regimens.

PubMed

Seeras, R C; Olatunbosun, O A; Pierson, R A; Turnell, R W

1995-01-01

To compare two dosage regimens for the administration of vaginal prostaglandin gel in triacetin base for induction of labor. Seventy subjects planned for elective induction of labor at term were randomized to treatment with PGE2 vaginal gel every 6 or 12 hours. The 6-hourly group received an initial dose of 1 mg, followed by 2 mg at 6 hour intervals for a maximum of two additional doses if not in active labor. The 12-hourly group had an initial dose of 2 mg followed by two additional doses at 12 hour intervals if not in active labor. Successful induction rate was higher in the 12-hourly as compared to 6-hourly gel regimen (100% vs. 91%, P > 0.05). Twelve hours after the initial dose, delivery occurred in 34% delivery had occurred in 57% and 37% respectively (P < 0.01). We found no difference in the induction-active labor interval (P > 0.05), and the induction-delivery interval (P > 0.05) between the two groups. Active labor followed a single dose of gel in 66% of the 12-hourly group compared to 40% of the 6-hourly group (P < 0.01). Syntocinon augmentation was needed in 6% of subjects in the 12-hourly group as compared to 26% in the 6-hourly group (P < 0.01). The cesarean section rate was similar in both groups. Uterine hyperstimulation occurred less frequently in the 12-hourly group (P < 0.05). The perinatal outcome was similar in both groups. The 12-hourly regimen was more effective than the 6-hourly regimen in initiating labor. The majority of the subjects in the 12 hourly group achieved labor following a single dose of gel. Induction delivery interval, however, was similar in both groups.

Duodenal and Other Gastrointestinal Toxicity in Cervical and Endometrial Cancer Treated With Extended-Field Intensity Modulated Radiation Therapy to Paraaortic Lymph Nodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poorvu, Philip D.; Sadow, Cheryl A.; Townamchai, Kanokpis

2013-04-01

Purpose: To characterize the rates of acute and late duodenal and other gastrointestinal (GI) toxicities among patients treated for cervical and endometrial cancers with extended-field intensity modulated radiation therapy (EF-IMRT) to the paraaortic nodes and to analyze dose-volume relationships of GI toxicities. Methods and Materials: Fifty-three patients with endometrial or cervical cancer underwent EF-IMRT to the paraaortic nodes, of whom 46 met the inclusion criteria for GI toxicity and 45 for duodenal toxicity analysis. The median prescribed dose to the paraaortic nodes was 54 Gy (range, 41.4-65 Gy). The 4 duodenal segments, whole duodenum, small bowel loops, peritoneum, and peritoneummore » plus retroperitoneal segments of colon were contoured retrospectively, and dosimetric analysis was performed to identify dose-volume relationships to grade ≥3 acute (<90 day) and late (≥90 day) GI toxicity. Results: Only 3/46 patients (6.5%) experienced acute grade ≥3 GI toxicity and 3/46 patients (6.5%) experienced late grade ≥3 GI toxicity. The median dose administered to these 6 patients was 50.4 Gy. One of 12 patients who received 63 to 65 Gy at the level of the renal hilum experienced grade 3 GI toxicity. Dosimetric analysis of patients with and without toxicity revealed no differences between the mean absolute or fractional volumes at any 5-Gy interval between 5 Gy and the maximum dose. None of the patients experienced duodenal toxicity. Conclusions: Treatment of paraaortic nodes with IMRT is associated with low rates of GI toxicities and no duodenal-specific toxicity, including patients treated with concurrent chemotherapy. This technique may allow sufficient dose sparing of the bowel to enable safe dose escalation to at least 65 Gy.« less

High dose rate brachytherapy source measurement intercomparison.

PubMed

Poder, Joel; Smith, Ryan L; Shelton, Nikki; Whitaker, May; Butler, Duncan; Haworth, Annette

2017-06-01

This work presents a comparison of air kerma rate (AKR) measurements performed by multiple radiotherapy centres for a single HDR 192 Ir source. Two separate groups (consisting of 15 centres) performed AKR measurements at one of two host centres in Australia. Each group travelled to one of the host centres and measured the AKR of a single 192 Ir source using their own equipment and local protocols. Results were compared to the 192 Ir source calibration certificate provided by the manufacturer by means of a ratio of measured to certified AKR. The comparisons showed remarkably consistent results with the maximum deviation in measurement from the decay-corrected source certificate value being 1.1%. The maximum percentage difference between any two measurements was less than 2%. The comparisons demonstrated the consistency of well-chambers used for 192 Ir AKR measurements in Australia, despite the lack of a local calibration service, and served as a valuable focal point for the exchange of ideas and dosimetry methods.

A Phase I Study of the Safety and Pharmacokinetics of Higher-Dose Icotinib in Patients With Advanced Non-Small Cell Lung Cancer

PubMed Central

Liu, Jian; Wu, Lihua; Wu, Guolan; Hu, Xingjiang; Zhou, Huili; Chen, Junchun; Zhu, Meixiang; Xu, Wei; Tan, Fenlai; Ding, Lieming; Wang, Yinxiang

2016-01-01

Lessons Learned This phase I study evaluated the maximum tolerated dose, dose-limiting toxicities, safety, pharmacokinetics, and efficacy of icotinib with a starting dose of 250 mg in pretreated, advanced non-small cell lung cancer patients. We observed a maximum tolerated dose of 500 mg with a favorable pharmacokinetics profile and antitumor activity. These findings provide clinicians with evidence for application of higher-dose icotinib. Background. Icotinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has shown favorable tolerability and antitumor activity at 100–200 mg in previous studies without reaching the maximum tolerated dose (MTD). In July 2011, icotinib was approved by the China Food and Drug Administration at a dose of 125 mg three times daily for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one platinum-based chemotherapy regimen. This study investigated the MTD, tolerability, and pharmacokinetics of higher-dose icotinib in patients with advanced NSCLC. Methods. Twenty-six patients with advanced NSCLC were treated at doses of 250–625 mg three times daily The EGFR mutation test was not mandatory in this study. Results. Twenty-four (92.3%) of 26 patients experienced at least one adverse event (AE); rash (61.5%), diarrhea (23.1%), and oral ulceration (11.5%) were most frequent AEs. Dose-limiting toxicities were seen in 2 of 6 patients in the 625-mg group, and the MTD was established at 500 mg. Icotinib was rapidly absorbed and eliminated. The amount of time that the drug was present at the maximum concentration in serum (Tmax) ranged from 1 to 3 hours (1.5–4 hours) after multiple doses. The t1/2 was similar after single- and multiple-dose administration (7.11 and 6.39 hours, respectively). A nonlinear relationship was observed between dose and drug exposure. Responses were seen in 6 (23.1%) patients, and 8 (30.8%) patients had stable disease. Conclusion. This study demonstrated that higher-dose icotinib was well-tolerated, with a MTD of 500 mg. Favorable antitumor activity and pharmacokinetic profile were observed in patients with heavily pretreated, advanced NSCLC. PMID:27789778

A Phase I Study of the Safety and Pharmacokinetics of Higher-Dose Icotinib in Patients With Advanced Non-Small Cell Lung Cancer.

PubMed

Liu, Jian; Wu, Lihua; Wu, Guolan; Hu, Xingjiang; Zhou, Huili; Chen, Junchun; Zhu, Meixiang; Xu, Wei; Tan, Fenlai; Ding, Lieming; Wang, Yinxiang; Shentu, Jianzhong

2016-11-01

This phase I study evaluated the maximum tolerated dose, dose-limiting toxicities, safety, pharmacokinetics, and efficacy of icotinib with a starting dose of 250 mg in pretreated, advanced non-small cell lung cancer patients. We observed a maximum tolerated dose of 500 mg with a favorable pharmacokinetics profile and antitumor activity.These findings provide clinicians with evidence for application of higher-dose icotinib. Icotinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has shown favorable tolerability and antitumor activity at 100-200 mg in previous studies without reaching the maximum tolerated dose (MTD). In July 2011, icotinib was approved by the China Food and Drug Administration at a dose of 125 mg three times daily for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one platinum-based chemotherapy regimen. This study investigated the MTD, tolerability, and pharmacokinetics of higher-dose icotinib in patients with advanced NSCLC. Twenty-six patients with advanced NSCLC were treated at doses of 250-625 mg three times daily The EGFR mutation test was not mandatory in this study. Twenty-four (92.3%) of 26 patients experienced at least one adverse event (AE); rash (61.5%), diarrhea (23.1%), and oral ulceration (11.5%) were most frequent AEs. Dose-limiting toxicities were seen in 2 of 6 patients in the 625-mg group, and the MTD was established at 500 mg. Icotinib was rapidly absorbed and eliminated. The amount of time that the drug was present at the maximum concentration in serum (T max ) ranged from 1 to 3 hours (1.5-4 hours) after multiple doses. The t 1/2 was similar after single- and multiple-dose administration (7.11 and 6.39 hours, respectively). A nonlinear relationship was observed between dose and drug exposure. Responses were seen in 6 (23.1%) patients, and 8 (30.8%) patients had stable disease. This study demonstrated that higher-dose icotinib was well-tolerated, with a MTD of 500 mg. Favorable antitumor activity and pharmacokinetic profile were observed in patients with heavily pretreated, advanced NSCLC. ©AlphaMed Press; the data published online to support this summary is the property of the authors.

Effective chemotherapy of heterogeneous and drug-resistant early colon cancers by intermittent dose schedules: a computer simulation study.

PubMed

Axelrod, David E; Vedula, Sudeepti; Obaniyi, James

2017-05-01

The effectiveness of cancer chemotherapy is limited by intra-tumor heterogeneity, the emergence of spontaneous and induced drug-resistant mutant subclones, and the maximum dose to which normal tissues can be exposed without adverse side effects. The goal of this project was to determine if intermittent schedules of the maximum dose that allows colon crypt maintenance could overcome these limitations, specifically by eliminating mixtures of drug-resistant mutants from heterogeneous early colon adenomas while maintaining colon crypt function. A computer model of cell dynamics in human colon crypts was calibrated with measurements of human biopsy specimens. The model allowed simulation of continuous and intermittent dose schedules of a cytotoxic chemotherapeutic drug, as well as the drug's effect on the elimination of mutant cells and the maintenance of crypt function. Colon crypts can tolerate a tenfold greater intermittent dose than constant dose. This allows elimination of a mixture of relatively drug-sensitive and drug-resistant mutant subclones from heterogeneous colon crypts. Mutants can be eliminated whether they arise spontaneously or are induced by the cytotoxic drug. An intermittent dose, at the maximum that allows colon crypt maintenance, can be effective in eliminating a heterogeneous mixture of mutant subclones before they fill the crypt and form an adenoma.

Radiation risk predictions for Space Station Freedom orbits

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Atwell, William; Weyland, Mark; Hardy, Alva C.; Wilson, John W.; Townsend, Lawrence W.; Shinn, Judy L.; Katz, Robert

1991-01-01

Risk assessment calculations are presented for the preliminary proposed solar minimum and solar maximum orbits for Space Station Freedom (SSF). Integral linear energy transfer (LET) fluence spectra are calculated for the trapped proton and GCR environments. Organ dose calculations are discussed using the computerized anatomical man model. The cellular track model of Katz is applied to calculate cell survival, transformation, and mutation rates for various aluminum shields. Comparisons between relative biological effectiveness (RBE) and quality factor (QF) values for SSF orbits are made.

SU-E-T-365: Dosimetric Impact of Dental Amalgam CT Image Artifacts On IMRT and VMAT Head and Neck Plans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cao, N; Young, L; Parvathaneni, U

Purpose: The presence of high density dental amalgam in patient CT image data sets causes dose calculation errors for head and neck (HN) treatment planning. This study assesses and compares dosimetric variations in IMRT and VMAT treatment plans due to dental artifacts. Methods: Sixteen HN patients with similar treatment sites (oropharynx), tumor volume and extensive dental artifacts were divided into two groups: IMRT (n=8, 6 to 9 beams) and VMAT (n=8, 2 arcs with 352° rotation). All cases were planned with the Pinnacle 9.2 treatment planning software using the collapsed cone convolution superposition algorithm and a range of prescription dosemore » from 60 to 72Gy. Two different treatment plans were produced, each based on one of two image sets: (a)uncorrected; (b)dental artifacts density overridden (set to 1.0g/cm{sup 3}). Differences between the two treatment plans for each of the IMRT and VMAT techniques were quantified by the following dosimetric parameters: maximum point dose, maximum spinal cord and brainstem dose, mean left and right parotid dose, and PTV coverage (V95%Rx). Average differences generated for these dosimetric parameters were compared between IMRT and VMAT plans. Results: The average absolute dose differences (plan a minus plan b) for the VMAT and IMRT techniques, respectively, caused by dental artifacts were: 2.2±3.3cGy vs. 37.6±57.5cGy (maximum point dose, P=0.15); 1.2±0.9cGy vs. 7.9±6.7cGy (maximum spinal cord dose, P=0.026); 2.2±2.4cGy vs. 12.1±13.0cGy (maximum brainstem dose, P=0.077); 0.9±1.1cGy vs. 4.1±3.5cGy (mean left parotid dose, P=0.038); 0.9±0.8cGy vs. 7.8±11.9cGy (mean right parotid dose, P=0.136); 0.021%±0.014% vs. 0.803%±1.44% (PTV coverage, P=0.17). Conclusion: For the HN plans studied, dental artifacts demonstrated a greater dose calculation error for IMRT plans compared to VMAT plans. Rotational arcs appear on the average to compensate dose calculation errors induced by dental artifacts. Thus, compared to VMAT, density overrides for dental artifacts are more important when planning IMRT of HN.« less

Dose Trends of Aripiprazole from 2004 to 2014 in Psychiatric Inpatients in Korea.

PubMed

Woo, Young Sup; Shim, In Hee; Lee, Sang-Yeol; Lee, Dae-Bo; Kim, Moon-Doo; Jung, Young-Eun; Lee, Jonghun; Won, Seunghee; Jon, Duk-In; Bahk, Won-Myong

2017-05-31

Although aripiprazole has been widely used to treat various psychiatric disorders, little is known about the adequate dosage for Asian patients in clinical practice. Hence, we evaluated the initial and maximum doses of aripiprazole from 2004 to 2014 to estimate the appropriate dosage for Korean psychiatric inpatients in clinical practice. In this retrospective study, we reviewed the medical records of patients who were hospitalized in five university hospitals in Korea from March 2004 to December 2014. The psychiatric diagnosis according to the text revision of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition during index hospitalization and the initial and maximum doses of aripiprazole were evaluated. There were 74 patients in Wave 1 (2004-2006), 201 patients in Wave 2 (2007-2010), and 353 patients in Wave 3 (2011-2014). The initial doses of aripiprazole in all diagnostic groups were significantly lower in Wave 3 than in Wave 2. The maximum doses of aripiprazole in each diagnostic group were not significantly different among Waves 1, 2, and 3. The relatively low initial doses of aripiprazole documented in our study may reflect a strategy by clinicians to minimize the side effects associated with aripiprazole use, such as akathisia.

Study Of Dose Distribution In A Human Body In Space Flight With The Spherical Tissue-Equivalent Phantom

NASA Astrophysics Data System (ADS)

Shurshakov, Vyacheslav; Akatov, Yu; Petrov, V.; Kartsev, I.; Polenov, Boris; Petrov, V.; Lyagushin, V.

In the space experiment MATROSHKA-R, the spherical tissue equivalent phantom (30 kg mass, 35 cm diameter and 10 cm central spherical cave) made in Russia has been installed in the star board crew cabin of the ISS Service Module. Due to the specially chosen phantom shape and size, the chord length distributions of the detector locations are attributed to self-shielding properties of the critical organs in a real human body. If compared with the anthropomorphic phantom Rando used inside and outside the ISS, the spherical phantom has lower mass, smaller size, and requires less crew time for the detector retrieval; its tissue-equivalent properties are closer to the standard human body tissue than the Rando-phantom material. In the first phase of the experiment the dose measurements were realized with only passive detectors (thermoluminescent and solid state track detectors). There were two experimental sessions with the spherical phantom in the crew cabin, (1) from Jan. 29, 2004 to Apr. 30, 2004 and (2) from Aug. 11, 2004 to Oct. 10, 2005. The detectors are placed inside the phantom along the axes of 20 containers and on the phantom outer surface in 32 pockets of the phantom jacket. The results obtained with the passive detectors returned to the ground after each session show the dose difference on the phantom surface as much as a factor of 2, the highest dose being observed close to the outer wall of the crew cabin, and the lowest dose being in the opposite location along the phantom diameter. Maximum dose rate measured in the phantom (0.31 mGy/day) is obviously due to the galactic cosmic ray (GCR) and Earth' radiation belt contribution on the ISS trajectory. Minimum dose rate (0.15 mGy/day) is caused mainly by the strongly penetrating GCR particles and is observed behind more than 5 g/cm2 tissue shielding. Critical organ doses, mean-tissue and effective doses of a crew member in the crew cabin are also estimated with the spherical phantom. The estimated effective dose rate (about 0.49 mSv/day at radiation quality factor of 2.6) is from 12 to 15 per cent lower than the averaged dose on the phantom surface as dependent on the body attitude.

Regulatory Forum Opinion Piece*: Retrospective Evaluation of Doses in the 26-week Tg.rasH2 Mice Carcinogenicity Studies: Recommendation to Eliminate High Doses at Maximum Tolerated Dose in Future Studies. A Response to the Counterpoints.

PubMed

Paranjpe, Madhav G; Denton, Melissa D; Vidmar, Tom J; Elbekai, Reem H

2016-01-01

We recently conducted a retrospective analysis of data collected from 29 Tg.rasH2 carcinogenicity studies conducted at our facility to determine how successful was the strategy of choosing the high dose of the 26-week studies based on an estimated maximum tolerated dose (MTD). As a result of our publication, 2 counterviews were expressed. Both counterviews illustrate very valid points in their interpretation of our data. In this article, we would like to highlight clarifications based on several points and issues they have raised in their papers, namely, the dose-level selection, determining if MTD was exceeded in 26-week studies, and a discussion on the number of dose groups to be used in the studies. © The Author(s) 2015.

TH-AB-201-12: Using Machine Log-Files for Treatment Planning and Delivery QA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stanhope, C; Liang, J; Drake, D

2016-06-15

Purpose: To determine the segment reduction and dose resolution necessary for machine log-files to effectively replace current phantom-based patient-specific quality assurance, while minimizing computational cost. Methods: Elekta’s Log File Convertor R3.2 records linac delivery parameters (dose rate, gantry angle, leaf position) every 40ms. Five VMAT plans [4 H&N, 1 Pulsed Brain] comprised of 2 arcs each were delivered on the ArcCHECK phantom. Log-files were reconstructed in Pinnacle on the phantom geometry using 1/2/3/4° control point spacing and 2/3/4mm dose grid resolution. Reconstruction effectiveness was quantified by comparing 2%/2mm gamma passing rates of the original and log-file plans. Modulation complexity scoresmore » (MCS) were calculated for each beam to correlate reconstruction accuracy and beam modulation. Percent error in absolute dose for each plan-pair combination (log-file vs. ArcCHECK, original vs. ArcCHECK, log-file vs. original) was calculated for each arc and every diode greater than 10% of the maximum measured dose (per beam). Comparing standard deviations of the three plan-pair distributions, relative noise of the ArcCHECK and log-file systems was elucidated. Results: The original plans exhibit a mean passing rate of 95.1±1.3%. The eight more modulated H&N arcs [MCS=0.088±0.014] and two less modulated brain arcs [MCS=0.291±0.004] yielded log-file pass rates most similar to the original plan when using 1°/2mm [0.05%±1.3% lower] and 2°/3mm [0.35±0.64% higher] log-file reconstructions respectively. Log-file and original plans displayed percent diode dose errors 4.29±6.27% and 3.61±6.57% higher than measurement. Excluding the phantom eliminates diode miscalibration and setup errors; log-file dose errors were 0.72±3.06% higher than the original plans – significantly less noisy. Conclusion: For log-file reconstructed VMAT arcs, 1° control point spacing and 2mm dose resolution is recommended, however, less modulated arcs may allow less stringent reconstructions. Following the aforementioned reconstruction recommendations, the log-file technique is capable of detecting delivery errors with equivalent accuracy and less noise than ArcCHECK QA. I am funded by an Elekta Research Grant.« less

Pembrolizumab Plus Pegylated Interferon alfa-2b or Ipilimumab for Advanced Melanoma or Renal Cell Carcinoma: Dose-Finding Results from the Phase Ib KEYNOTE-029 Study.

PubMed

Atkins, Michael B; Hodi, F Stephen; Thompson, John A; McDermott, David F; Hwu, Wen-Jen; Lawrence, Donald P; Dawson, Nancy A; Wong, Deborah J; Bhatia, Shailender; James, Marihella; Jain, Lokesh; Robey, Seth; Shu, Xinxin; Homet Moreno, Blanca; Perini, Rodolfo F; Choueiri, Toni K; Ribas, Antoni

2018-04-15

Purpose: Pembrolizumab monotherapy, ipilimumab monotherapy, and pegylated interferon alfa-2b (PEG-IFN) monotherapy are active against melanoma and renal cell carcinoma (RCC). We explored the safety and preliminary antitumor activity of pembrolizumab combined with either ipilimumab or PEG-IFN in patients with advanced melanoma or RCC. Experimental Design: The phase Ib KEYNOTE-029 study (ClinicalTrials.gov, NCT02089685) included independent pembrolizumab plus reduced-dose ipilimumab and pembrolizumab plus PEG-IFN cohorts. Pembrolizumab 2 mg/kg every 3 weeks (Q3W) plus 4 doses of ipilimumab 1 mg/kg Q3W was tolerable if ≤6 of 18 patients experienced a dose-limiting toxicity (DLT). The target DLT rate for pembrolizumab 2 mg/kg Q3W plus PEG-IFN was 30%, with a maximum of 14 patients per dose level. Response was assessed per RECIST v1.1 by central review. Results: The ipilimumab cohort enrolled 22 patients, including 19 evaluable for DLTs. Six patients experienced ≥1 DLT. Grade 3 to 4 treatment-related adverse events occurred in 13 (59%) patients. Responses occurred in 5 of 12 (42%) patients with melanoma and 3 of 10 (30%) patients with RCC. In the PEG-IFN cohort, DLTs occurred in 2 of 14 (14%) patients treated at dose level 1 (PEG-IFN 1 μg/kg/week) and 2 of 3 (67%) patients treated at dose level 2 (PEG-IFN 2 μg/kg/week). Grade 3 to 4 treatment-related adverse events occurred in 10 of 17 (59%) patients. Responses occurred in 1 of 5 (20%) patients with melanoma and 2 of 12 (17%) patients with RCC. Conclusions: Pembrolizumab 2 mg/kg Q3W plus ipilimumab 1 mg/kg Q3W was tolerable and provided promising antitumor activity in patients with advanced melanoma or RCC. The maximum tolerated dose of pembrolizumab plus PEG-IFN had limited antitumor activity in this population. Clin Cancer Res; 24(8); 1805-15. ©2018 AACR . ©2018 American Association for Cancer Research.

Phase I dose-escalation studies of roniciclib, a pan-cyclin-dependent kinase inhibitor, in advanced malignancies.

PubMed

Bahleda, Rastislav; Grilley-Olson, Juneko E; Govindan, Ramaswamy; Barlesi, Fabrice; Greillier, Laurent; Perol, Maurice; Ray-Coquard, Isabelle; Strumberg, Dirk; Schultheis, Beate; Dy, Grace K; Zalcman, Gérard; Weiss, Glen J; Walter, Annette O; Kornacker, Martin; Rajagopalan, Prabhu; Henderson, David; Nogai, Hendrik; Ocker, Matthias; Soria, Jean-Charles

2017-06-06

To evaluate safety, pharmacokinetics, and maximum tolerated dose of roniciclib in patients with advanced malignancies, with dose expansion to evaluate clinical benefit at the recommended phase II dose (RP2D). Two phase I dose-escalation studies evaluated two roniciclib dosing schedules: 3 days on/4 days off or 4 weeks on/2 weeks off. The expansion phase included patients with small-cell lung cancer (SCLC), ovarian cancer, or tumour mutations involving the CDK signalling pathway. Ten patients were evaluable in the 4 weeks on/2 weeks off schedule (terminated following limited tolerability) and 47 in the 3 days on/4 days off schedule dose-escalation cohorts. On the 3 days on/4 days off schedule, RP2D was 5 mg twice daily in solid tumours (n=40); undetermined in lymphoid malignancies (n=7). Common roniciclib-related adverse events included nausea (76.6%), fatigue (65.8%), diarrhoea (63.1%), and vomiting (57.7%). Roniciclib demonstrated rapid absorption and dose-proportional increase in exposure. One partial response (1.0%) was observed. In RP2D expansion cohorts, the disease control rate (DCR) was 40.9% for patients with ovarian cancer (n=25), 17.4% for patients with SCLC (n=33), and 33.3% for patients with CDK-related tumour mutations (n=6). Roniciclib demonstrated an acceptable safety profile and moderate DCR in 3 days on/4 days off schedule.

Dosimetric impact of an air passage on intraluminal brachytherapy for bronchus cancer.

PubMed

Okamoto, Hiroyuki; Wakita, Akihisa; Nakamura, Satoshi; Nishioka, Shie; Aikawa, Ako; Kato, Toru; Abe, Yoshihisa; Kobayashi, Kazuma; Inaba, Koji; Murakami, Naoya; Itami, Jun

2016-11-01

The brachytherapy dose calculations used in treatment planning systems (TPSs) have conventionally been performed assuming homogeneous water. Using measurements and a Monte Carlo simulation, we evaluated the dosimetric impact of an air passage on brachytherapy for bronchus cancer. To obtain the geometrical characteristics of an air passage, we analyzed the anatomical information from CT images of patients who underwent intraluminal brachytherapy using a high-dose-rate 192 Ir source (MicroSelectron V2r®, Nucletron). Using an ionization chamber, we developed a measurement system capable of measuring the peripheral dose with or without an air cavity surrounding the catheter. Air cavities of five different radii (0.3, 0.5, 0.75, 1.25 and 1.5 cm) were modeled by cylindrical tubes surrounding the catheter. A Monte Carlo code (GEANT4) was also used to evaluate the dosimetric impact of the air cavity. Compared with dose calculations in homogeneous water, the measurements and GEANT4 indicated a maximum overdose of 5-8% near the surface of the air cavity (with the maximum radius of 1.5 cm). Conversely, they indicated a minimum overdose of ~1% in the region 3-5 cm from the cavity surface for the smallest radius of 0.3 cm. The dosimetric impact depended on the size and the distance of the air passage, as well as the length of the treatment region. Based on dose calculations in water, the TPS for intraluminal brachytherapy for bronchus cancer had an unexpected overdose of 3-5% for a mean radius of 0.75 cm. This study indicates the need for improvement in dose calculation accuracy with respect to intraluminal brachytherapy for bronchus cancer. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

A novel predictive pharmacokinetic/pharmacodynamic model of repolarization prolongation derived from the effects of terfenadine, cisapride and E-4031 in the conscious chronic av node--ablated, His bundle-paced dog.

PubMed

Nolan, Emily R; Feng, Meihua Rose; Koup, Jeffrey R; Liu, Jing; Turluck, Daniel; Zhang, Yiqun; Paulissen, Jerome B; Olivier, N Bari; Miller, Teresa; Bailie, Marc B

2006-01-01

Terfenadine, cisapride, and E-4031, three drugs that prolong ventricular repolarization, were selected to evaluate the sensitivity of the conscious chronic atrioventricular node--ablated, His bundle-paced Dog for defining drug induced cardiac repolarization prolongation. A novel predictive pharmacokinetic/pharmacodynamic model of repolarization prolongation was generated from these data. Three male beagle dogs underwent radiofrequency AV nodal ablation, and placement of a His bundle-pacing lead and programmable pacemaker under anesthesia. Each dog was restrained in a sling for a series of increasing dose infusions of each drug while maintained at a constant heart rate of 80 beats/min. RT interval, a surrogate for QT interval in His bundle-paced dogs, was recorded throughout the experiment. E-4031 induced a statistically significant RT prolongation at the highest three doses. Cisapride resulted in a dose-dependent increase in RT interval, which was statistically significant at the two highest doses. Terfenadine induced a dose-dependent RT interval prolongation with a statistically significant change occurring only at the highest dose. The relationship between drug concentration and RT interval change was described by a sigmoid E(max) model with an effect site. Maximum RT change (E(max)), free drug concentration at half of the maximum effect (EC(50)), and free drug concentration associated with a 10 ms RT prolongation (EC(10 ms)) were estimated. A linear correlation between EC(10 ms) and HERG IC(50) values was identified. The conscious dog with His bundle-pacing detects delayed cardiac repolarization related to I(Kr) inhibition, and detects repolarization change induced by drugs with activity at multiple ion channels. A clinically relevant sensitivity and a linear correlation with in vitro HERG data make the conscious His bundle-paced dog a valuable tool for detecting repolarization effect of new chemical entities.

SU-F-T-22: Clinical Implications When Using TG-186 (ACE) Heterogeneity Software

DOE Office of Scientific and Technical Information (OSTI.GOV)

Likhacheva, A; Grade, E; Sadeghi, A

Purpose: The purpose of this study is to compare dosimetric calculations using traditional TG-43 formalism and Oncentra Brachy Advanced Collapsed cone Engine (ACE) TG-186 calculation algorithm in clinical setting. Methods: We analyzed dosimetry of four patients treated with accelerated partial breast irradiation using a multi-channel intracavitary device (SAVI). All patients were treated to 34 Gy in 10 fractions using a high-dose-rate (192) Ir source. The plans were designed and treated using the TG-43 model. ACE was used to assess the effect heterogeneity correction on various dosimetric parameters. Mass density was estimated using Hounsfield units. Results: Compared to TG-43 formalism, ACEmore » estimated lower doses to targets and organs at risk. The mean difference was 19.8% (range 15.3–24.1%) for PTV-eval V200, 12.0% (range 9.7–17.7%) for PTV-eval V150, 4.3% (range 3.3–6.5%) for PTV-eval D95, 3.3% (range 1.4–5.4%) for PTV-eval D90, 5.4% (range 2.9–9.9%) for maximum rib dose, and 5.7% (2.4–7.4%) for maximum skin dose. There was no correlation between the magnitude of the difference and the PTV-eval volume, air volume, or tissue-applicator conformance. Conclusion: Based on our preliminary study, the TG-43 algorithm appears to overestimate the dose to targets and organs at risk when compared to the ACE TG-186 software. We hypothesize that air adjacent to the SAVI struts contributes to lack of scatter thereby contributing a significant difference in dose calculation when using ACE. We believe that ACE calculation provides a more realistic isodose distribution than TG-43. We plan to further investigate the impact of heterogeneity correction on brachytherapy planning for a wide variety of clinical scenarios, include skin, cervix/uterus, prostate, and lung.« less

Effect of photon energy spectrum on dosimetric parameters of brachytherapy sources.

PubMed

Ghorbani, Mahdi; Mehrpouyan, Mohammad; Davenport, David; Ahmadi Moghaddas, Toktam

2016-06-01

The aim of this study is to quantify the influence of the photon energy spectrum of brachytherapy sources on task group No. 43 (TG-43) dosimetric parameters. Different photon spectra are used for a specific radionuclide in Monte Carlo simulations of brachytherapy sources. MCNPX code was used to simulate 125I, 103Pd, 169Yb, and 192Ir brachytherapy sources. Air kerma strength per activity, dose rate constant, radial dose function, and two dimensional (2D) anisotropy functions were calculated and isodose curves were plotted for three different photon energy spectra. The references for photon energy spectra were: published papers, Lawrence Berkeley National Laboratory (LBNL), and National Nuclear Data Center (NNDC). The data calculated by these photon energy spectra were compared. Dose rate constant values showed a maximum difference of 24.07% for 103Pd source with different photon energy spectra. Radial dose function values based on different spectra were relatively the same. 2D anisotropy function values showed minor differences in most of distances and angles. There was not any detectable difference between the isodose contours. Dosimetric parameters obtained with different photon spectra were relatively the same, however it is suggested that more accurate and updated photon energy spectra be used in Monte Carlo simulations. This would allow for calculation of reliable dosimetric data for source modeling and calculation in brachytherapy treatment planning systems.

Effect of photon energy spectrum on dosimetric parameters of brachytherapy sources

PubMed Central

Ghorbani, Mahdi; Davenport, David

2016-01-01

Abstract Aim The aim of this study is to quantify the influence of the photon energy spectrum of brachytherapy sources on task group No. 43 (TG-43) dosimetric parameters. Background Different photon spectra are used for a specific radionuclide in Monte Carlo simulations of brachytherapy sources. Materials and methods MCNPX code was used to simulate 125I, 103Pd, 169Yb, and 192Ir brachytherapy sources. Air kerma strength per activity, dose rate constant, radial dose function, and two dimensional (2D) anisotropy functions were calculated and isodose curves were plotted for three different photon energy spectra. The references for photon energy spectra were: published papers, Lawrence Berkeley National Laboratory (LBNL), and National Nuclear Data Center (NNDC). The data calculated by these photon energy spectra were compared. Results Dose rate constant values showed a maximum difference of 24.07% for 103Pd source with different photon energy spectra. Radial dose function values based on different spectra were relatively the same. 2D anisotropy function values showed minor differences in most of distances and angles. There was not any detectable difference between the isodose contours. Conclusions Dosimetric parameters obtained with different photon spectra were relatively the same, however it is suggested that more accurate and updated photon energy spectra be used in Monte Carlo simulations. This would allow for calculation of reliable dosimetric data for source modeling and calculation in brachytherapy treatment planning systems. PMID:27247558

Dose-volume histogram analysis of brainstem necrosis in head and neck tumors treated using carbon-ion radiotherapy.

PubMed

Shirai, Katsuyuki; Fukata, Kyohei; Adachi, Akiko; Saitoh, Jun-Ichi; Musha, Atsushi; Abe, Takanori; Kanai, Tatsuaki; Kobayashi, Daijiro; Shigeta, Yuka; Yokoo, Satoshi; Chikamatsu, Kazuaki; Ohno, Tatsuya; Nakano, Takashi

2017-10-01

We aimed to evaluate the relationship between brainstem necrosis and dose-volume histograms in patients with head and neck tumors after carbon-ion radiotherapy. We evaluated 85 patients with head and neck tumors who underwent carbon-ion radiotherapy and were followed-up for ≥12months. Brainstem necrosis was evaluated using the Common Terminology Criteria for Adverse Events (version 4.0). The median follow-up was 24months, and four patients developed grade 1 brainstem necrosis, with 2-year and 3-year cumulative rates of 2.8% and 6.5%, respectively. Receiver operating characteristic curve analysis revealed the following significant cut-off values: a maximum brainstem dose of 48Gy (relative biological effectiveness [RBE]), D1cm 3 of 27Gy (RBE), V40Gy (RBE) of 0.1cm 3 , V30Gy (RBE) of 0.7cm 3 , and V20Gy (RBE) of 1.4cm 3 . Multivariate analysis revealed that V30Gy (RBE) was most significantly associated with brainstem necrosis. The 2-year cumulative rates were 33% and 0% for V30Gy (RBE) of ≥0.7cm 3 and <0.7cm 3 , respectively (p<0.001). The present study indicated that the dose constraints might help minimize brainstem necrosis after carbon-ion radiotherapy. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Phase I/II trial of doxorubicin and fixed dose-rate infusion gemcitabine in advanced soft tissue sarcomas: a GEIS study

PubMed Central

López-Pousa, A; Losa, R; Martín, J; Maurel, J; Fra, J; Sierra, M; Casado, A; García del Muro, J; Poveda, A; Balañá, C; Martínez-Trufero, J; Esteban, E; Buesa, J M

2006-01-01

The aim of the study was to determine the dose-limiting toxicity and maximum tolerated dose of a first-line combination of doxorubicin and gemcitabine in adult patients with advanced soft tissue sarcomas and to explore its activity and toxicity, and the presence of possible interactions between these agents. Patients with measurable disease were initially treated with doxorubicin 60 mg m−2 by i.v. bolus on day 1 followed by gemcitabine at 800 mg m−2 over 80 min on days 1 and 8, every 21 days. Concentrations of gemcitabine and 2′,2′-difluorodeoxyuridine in plasma, and gemcitabine triphosphate levels in peripheral blood mononuclear cells were determined during 8 h after the start of gemcitabine infusion. Myelosuppression and stomatitis were limiting toxicities, and the initial dose level was applied for the Phase II trial, where grade 3–4 granulocytopenia occurred in 70% of patients, grade 3 stomatitis in 46% and febrile neutropenia in 20%. Objective activity in 36 patients was 22% (95% CI: 9–35%), and a 50% remission rate was noted in leiomyosarcomas. Administration of doxorubicin preceding gemcitabine significantly reduced the synthesis of gemcitabine triphosphate. Clinical activity, similar to that of single-agent doxorubicin, and the toxicity encountered do not justify further studies with this schedule of administration. PMID:16721358

Monte Carlo and Phantom Study of the Radiation Dose to the Body from Dedicated Computed Tomography of the Breast

PubMed Central

Sechopoulos, Ioannis; Vedantham, Srinivasan; Suryanarayanan, Sankararaman; D’Orsi, Carl J.; Karellas, Andrew

2008-01-01

Purpose To prospectively determine the radiation dose absorbed by the organs and tissues of the body during a dedicated computed tomography of the breast (DBCT) study using Monte Carlo methods and a phantom. Materials and Methods Using the Geant4 Monte Carlo toolkit, the Cristy anthropomorphic phantom and the geometry of a prototype DBCT was simulated. The simulation was used to track x-rays emitted from the source until their complete absorption or exit from the simulation limits. The interactions of the x-rays with the 65 different volumes representing organs, bones and other tissues of the anthropomorphic phantom that resulted in energy deposition were recorded. These data were used to compute the radiation dose to the organs and tissues during a complete DBCT acquisition relative to the average glandular dose to the imaged breast (ROD, relative organ dose), using the x-ray spectra proposed for DBCT imaging. The effectiveness of a lead shield for reducing the dose to the organs was investigated. Results The maximum ROD among the organs was for the ipsilateral lung with a maximum of 3.25%, followed by the heart and the thymus. Of the skeletal tissues, the sternum received the highest dose with a maximum ROD to the bone marrow of 2.24%, and to the bone surface of 7.74%. The maximum ROD to the uterus, representative of that of an early-stage fetus, was 0.026%. These maxima occurred for the highest energy x-ray spectrum (80 kVp) analyzed. A lead shield does not protect substantially the organs that receive the highest dose from DBCT. Discussion Although the dose to the organs from DBCT is substantially higher than that from planar mammography, they are comparable or considerably lower than those reached by other radiographic procedures and much lower than other CT examinations. PMID:18292479

Use of iodine for water disinfection: iodine toxicity and maximum recommended dose.

PubMed Central

Backer, H; Hollowell, J

2000-01-01

Iodine is an effective, simple, and cost-efficient means of water disinfection for people who vacation, travel, or work in areas where municipal water treatment is not reliable. However, there is considerable controversy about the maximum safe iodine dose and duration of use when iodine is ingested in excess of the recommended daily dietary amount. The major health effect of concern with excess iodine ingestion is thyroid disorders, primarily hypothyroidism with or without iodine-induced goiter. A review of the human trials on the safety of iodine ingestion indicates that neither the maximum recommended dietary dose (2 mg/day) nor the maximum recommended duration of use (3 weeks) has a firm basis. Rather than a clear threshold response level or a linear and temporal dose-response relationship between iodine intake and thyroid function, there appears to be marked individual sensitivity, often resulting from unmasking of underlying thyroid disease. The use of iodine for water disinfection requires a risk-benefit decision based on iodine's benefit as a disinfectant and the changes it induces in thyroid physiology. By using appropriate disinfection techniques and monitoring thyroid function, most people can use iodine for water treatment over a prolonged period of time. PMID:10964787

SU-E-J-80: Interplay Effect Between VMAT Intensity Modulation and Tumor Motion in Hypofractioned Lung Treatment, Investigated with 3D Pressage Dosimeter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Touch, M; Duke University Medical Center, Durham, NC; Wu, Q

2014-06-01

Purpose: To demonstrate an embedded tissue equivalent presage dosimeter for measuring 3D doses in moving tumors and to study the interplay effect between the tumor motion and intensity modulation in hypofractioned Volumetric Modulated Arc Therapy(VMAT) lung treatment. Methods: Motion experiments were performed using cylindrical Presage dosimeters (5cm diameter by 7cm length) mounted inside the lung insert of a CIRS thorax phantom. Two different VMAT treatment plans were created and delivered in three different scenarios with the same prescribed dose of 18 Gy. Plan1, containing a 2 centimeter spherical CTV with an additional 2mm setup margin, was delivered on a stationarymore » phantom. Plan2 used the same CTV except expanded by 1 cm in the Sup-Inf direction to generate ITV and PTV respectively. The dosimeters were irradiated in static and variable motion scenarios on a Truebeam system. After irradiation, high resolution 3D dosimetry was performed using the Duke Large Field-of-view Optical-CT Scanner, and compared to the calculated dose from Eclipse. Results: In the control case (no motion), good agreement was observed between the planned and delivered dose distributions as indicated by 100% 3D Gamma (3% of maximum planned dose and 3mm DTA) passing rates in the CTV. In motion cases gamma passing rates was 99% in CTV. DVH comparisons also showed good agreement between the planned and delivered dose in CTV for both control and motion cases. However, differences of 15% and 5% in dose to PTV were observed in the motion and control cases respectively. Conclusion: With very high dose nature of a hypofraction treatment, significant effect was observed only motion is introduced to the target. This can be resulted from the motion of the moving target and the modulation of the MLC. 3D optical dosimetry can be of great advantage in hypofraction treatment dose validation studies.« less

Dosimetric validation and clinical implementation of two 3D dose verification systems for quality assurance in volumetric-modulated arc therapy techniques.

PubMed

Clemente-Gutiérrez, Francisco; Pérez-Vara, Consuelo

2015-03-08

A pretreatment quality assurance program for volumetric techniques should include redundant calculations and measurement-based verifications. The patient-specific quality assurance process must be based in clinically relevant metrics. The aim of this study was to show the commission, clinical implementation, and comparison of two systems that allow performing a 3D redundant dose calculation. In addition, one of them is capable of reconstructing the dose on patient anatomy from measurements taken with a 2D ion chamber array. Both systems were compared in terms of reference calibration data (absolute dose, output factors, percentage depth-dose curves, and profiles). Results were in good agreement for absolute dose values (discrepancies were below 0.5%) and output factors (mean differences were below 1%). Maximum mean discrepancies were located between 10 and 20 cm of depth for PDDs (-2.7%) and in the penumbra region for profiles (mean DTA of 1.5 mm). Validation of the systems was performed by comparing point-dose measurements with values obtained by the two systems for static, dynamic fields from AAPM TG-119 report, and 12 real VMAT plans for different anatomical sites (differences better than 1.2%). Comparisons between measurements taken with a 2D ion chamber array and results obtained by both systems for real VMAT plans were also performed (mean global gamma passing rates better than 87.0% and 97.9% for the 2%/2 mm and 3%/3 mm criteria). Clinical implementation of the systems was evaluated by comparing dose-volume parameters for all TG-119 tests and real VMAT plans with TPS values (mean differences were below 1%). In addition, comparisons between dose distributions calculated by TPS and those extracted by the two systems for real VMAT plans were also performed (mean global gamma passing rates better than 86.0% and 93.0% for the 2%/2 mm and 3%/ 3 mm criteria). The clinical use of both systems was successfully evaluated.

Image-Guided High-Dose Rate Brachytherapy in Cervix Carcinoma Using Balloon Catheter and Belt Immobilization System.

PubMed

Fan, Qiyong; Yeung, Anamaria R; Amdur, Robert; Helmig, Richard; Park, Justin; Li, Jonathan; Kahler, Darren; Liu, Chihray; Lu, Bo

2017-06-01

The efficacy of image-guided high-dose rate brachytherapy for cervical cancer is limited by the ineffective rectal sparing devices available commercially and the potential applicator movement. We developed a novel device using a balloon catheter and a belt immobilization system, serving for rectal dose reduction and applicator immobilization purposes, respectively. The balloon catheter is constructed by gluing a short inflatable tube to a long regular open-end catheter. Contrast agent (10) cm 3 is injected into the inflatable end, which is affixed to the tandem and ring applicator, to displace the posterior vaginal wall. The belt immobilization system consists of a specially designed bracket that can hold and fix itself to the applicator, a diaper-like Velcro fastener package used for connecting the patient's pelvis to the bracket, and a buckle that holds the fasteners to stabilize the whole system. The treatment data for 21 patients with cervical cancer using both balloon catheter and belt immobilization system were retrospectively analyzed. Computed tomography and magnetic resonance images, acquired about 30 minutes apart, were registered to evaluate the effectiveness of the immobilization system. In comparison with a virtual rectal blade, the balloon decreased the rectal point dose by 34% ± 4.2% (from 276 ± 57 to 182 ± 38 cGy), corresponding to an extra sparing distance of 7.9 ± 1.1 mm. The maximum sparing distance variation per patient is 1.4 ± 0.6 mm, indicating the high interfractional reproducibility for rectum sparing. With the immobilization system, the mean translational and rotational displacements of the applicator set are <3 mm and <1.5°, respectively, in all directions. The rectal balloon provides significant dose reduction to the rectum and it may potentially minimize patient discomfort. The immobilization system permits almost no movement of the applicator during treatment. This work has the potential to be promoted as a standardized solution for high-dose rate treatment of cervical cancer.

TH-C-12A-04: Dosimetric Evaluation of a Modulated Arc Technique for Total Body Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsiamas, P; Czerminska, M; Makrigiorgos, G

2014-06-15

Purpose: A simplified Total Body Irradiation (TBI) was developed to work with minimal requirements in a compact linac room without custom motorized TBI couch. Results were compared to our existing fixed-gantry double 4 MV linac TBI system with prone patient and simultaneous AP/PA irradiation. Methods: Modulated arc irradiates patient positioned in prone/supine positions along the craniocaudal axis. A simplified inverse planning method developed to optimize dose rate as a function of gantry angle for various patient sizes without the need of graphical 3D treatment planning system. This method can be easily adapted and used with minimal resources. Fixed maximum fieldmore » size (40×40 cm2) is used to decrease radiation delivery time. Dose rate as a function of gantry angle is optimized to result in uniform dose inside rectangular phantoms of various sizes and a custom VMAT DICOM plans were generated using a DICOM editor tool. Monte Carlo simulations, film and ionization chamber dosimetry for various setups were used to derive and test an extended SSD beam model based on PDD/OAR profiles for Varian 6EX/ TX. Measurements were obtained using solid water phantoms. Dose rate modulation function was determined for various size patients (100cm − 200cm). Depending on the size of the patient arc range varied from 100° to 120°. Results: A PDD/OAR based beam model for modulated arc TBI therapy was developed. Lateral dose profiles produced were similar to profiles of our existing TBI facility. Calculated delivery time and full arc depended on the size of the patient (∼8min/ 100° − 10min/ 120°, 100 cGy). Dose heterogeneity varied by about ±5% − ±10% depending on the patient size and distance to the surface (buildup region). Conclusion: TBI using simplified modulated arc along craniocaudal axis of different size patients positioned on the floor can be achieved without graphical / inverse 3D planning.« less

Advantages of concurrent biochemotherapy modified by decrescendo interleukin-2, granulocyte colony-stimulating factor, and tamoxifen for patients with metastatic melanoma.

PubMed

O'Day, S J; Gammon, G; Boasberg, P D; Martin, M A; Kristedja, T S; Guo, M; Stern, S; Edwards, S; Fournier, P; Weisberg, M; Cannon, M; Fawzy, N W; Johnson, T D; Essner, R; Foshag, L J; Morton, D L

1999-09-01

Concurrent biochemotherapy results in high response rates but also significant toxicity in patients with metastatic melanoma. We attempted to improve its efficacy and decrease its toxicity by using decrescendo dosing of interleukin-2 (IL-2), posttreatment granulocyte colony-stimulating factor (G-CSF), and low-dose tamoxifen. Forty-five patients with poor prognosis metastatic melanoma were treated at a community hospital inpatient oncology unit affiliated with the John Wayne Cancer Institute (Santa Monica, CA) between July 1995 and September 1997. A 5-day modified concurrent biochemotherapy regimen of dacarbazine, vinblastine, cisplatin, decrescendo IL-2, interferon alfa-2b, and tamoxifen was repeated at 21-day intervals. G-CSF was administered beginning on day 6 for 7 to 10 days. The overall response rate was 57% (95% confidence interval, 42% to 72%), the complete response rate was 23%, and the partial response rate was 34%. Complete remissions were achieved in an additional 11% of patients by surgical resection of residual disease after biochemotherapy. The median time to progression was 6.3 months and the median duration of survival was 11.4 months. At a maximum follow-up of 36 months (range, 10 to 36 months), 32% of patients are alive and 14% remain free of disease. Decrescendo IL-2 dosing and administration of G-CSF seemed to reduce toxicity, length of hospital stay, and readmission rates. No patient required intensive care unit monitoring, and there were no treatment-related deaths. The data from this study indicate that the modified concurrent biochemotherapy regimen reduces the toxicity of concurrent biochemotherapy with no apparent decrease in response rate in patients with poor prognosis metastatic melanoma.

Dosimetric evaluation of a MOSFET detector for clinical application in photon therapy.

PubMed

Kohno, Ryosuke; Hirano, Eriko; Nishio, Teiji; Miyagishi, Tomoko; Goka, Tomonori; Kawashima, Mitsuhiko; Ogino, Takashi

2008-01-01

Dosimetric characteristics of a metal oxide-silicon semiconductor field effect transistor (MOSFET) detector are studied with megavoltage photon beams for patient dose verification. The major advantages of this detector are its size, which makes it a point dosimeter, and its ease of use. In order to use the MOSFET detector for dose verification of intensity-modulated radiation therapy (IMRT) and in-vivo dosimetry for radiation therapy, we need to evaluate the dosimetric properties of the MOSFET detector. Therefore, we investigated the reproducibility, dose-rate effect, accumulated-dose effect, angular dependence, and accuracy in tissue-maximum ratio measurements. Then, as it takes about 20 min in actual IMRT for the patient, we evaluated fading effect of MOSFET response. When the MOSFETs were read-out 20 min after irradiation, we observed a fading effect of 0.9% with 0.9% standard error of the mean. Further, we applied the MOSFET to the measurement of small field total scatter factor. The MOSFET for dose measurements of small field sizes was better than the reference pinpoint chamber with vertical direction. In conclusion, we assessed the accuracy, reliability, and usefulness of the MOSFET detector in clinical applications such as pinpoint absolute dosimetry for small fields.

Is it possible to avoid hypopituitarism after irradiation of pituitary adenomas by the Leksell gamma knife?

PubMed

Marek, Josef; Jezková, Jana; Hána, Václav; Krsek, Michal; Bandúrová, L'ubomíra; Pecen, Ladislav; Vladyka, Vilibald; Liscák, Roman

2011-02-01

Radiation therapy is one of the treatment options for pituitary adenomas. The most common side effect associated with Leksell gamma knife (LGK) irradiation is the development of hypopituitarism. The aim of this study was to verify that hypopituitarism does not develop if the maximum mean dose to pituitary is kept under 15 Gy and to evaluate the influence of maximum distal infundibulum dose on the development of hypopituitarism. We followed the incidence of hypopituitarism in 85 patients irradiated with LGK in 1993-2003. The patients were divided in two subgroups: the first subgroup followed prospectively (45 patients), irradiated with a mean dose to pituitary <15 Gy; the second subgroup followed retrospectively 1993-2001 and prospectively 2001-2009 (40 patients), irradiated with a mean dose to pituitary >15 Gy. Serum TSH, free thyroxine, testosterone or 17β-oestradiol, IGF1, prolactin and cortisol levels were evaluated before and every 6 months after LGK irradiation. Hypopituitarism after LGK irradiation developed only in 1 out of 45 (2.2%) patients irradiated with a mean dose to pituitary <15 Gy, in contrast to 72.5% patients irradiated with a mean dose to pituitary >15 Gy. The radiation dose to the distal infundibulum was found as an independent factor of hypopituitarism with calculated maximum safe dose of 17 Gy. Keeping the mean radiation dose to pituitary under 15 Gy and the dose to the distal infundibulum under 17 Gy prevents the development of hypopituitarism following LGK irradiation.

A phase I trial of two sequence-specific schedules of decitabine and vorinostat in patients with acute myeloid leukemia

PubMed Central

How, Jonathan; Minden, Mark D.; Brian, Leber; Chen, Eric X.; Brandwein, Joseph; Schuh, Andre C.; Schimmer, Aaron D.; Gupta, Vikas; Webster, Sheila; Degelder, Tammy; Haines, Patricia; Stayner, Lee-Anne; McGill, Shauna; Wang, Lisa; Piekarz, Richard; Wong, Tracy; Siu, Lillian L.; Espinoza-Delgado, Igor; Holleran, Julianne L.; Egorin, Merrill J.; Yee, Karen W. L.

2015-01-01

This phase I trial evaluated two schedules of escalating vorinostat in combination with decitabine every 28 days: (i) sequential or (ii) concurrent. There were three dose-limiting toxicities: grade 3 fatigue and generalized muscle weakness on the sequential schedule (n = 1) and grade 3 fatigue on the concurrent schedule (n = 2). The maximum tolerated dose was not reached on both planned schedules. The overall response rate (ORR) was 23% (three complete response [CR], two CR with incomplete incomplete blood count recovery [CRi], one partial response [PR] and two morphological leukemic free state [MLFS]). The ORR for all and previously untreated patients in the sequential arm was 13% (one CRi; one MLFS) and 0% compared to 30% (three CR; one CRi; one PR; one MLFS) and 36% in the concurrent arm (p = 0.26 for both), respectively. Decitabine plus vorinostat was safe and has clinical activity in patients with previously untreated acute myeloid leukemia. Responses appear higher with the concurrent dose schedule. Cumulative toxicities may limit long-term usage on the current dose/schedules. PMID:25682963

DOSIMETRIC CONSEQUENCES OF USING CONTRAST-ENHANCED COMPUTED TOMOGRAPHIC IMAGES FOR INTENSITY-MODULATED STEREOTACTIC BODY RADIOTHERAPY PLANNING.

PubMed

Yoshikawa, Hiroto; Roback, Donald M; Larue, Susan M; Nolan, Michael W

2015-01-01

Potential benefits of planning radiation therapy on a contrast-enhanced computed tomography scan (ceCT) should be weighed against the possibility that this practice may be associated with an inadvertent risk of overdosing nearby normal tissues. This study investigated the influence of ceCT on intensity-modulated stereotactic body radiotherapy (IM-SBRT) planning. Dogs with head and neck, pelvic, or appendicular tumors were included in this retrospective cross-sectional study. All IM-SBRT plans were constructed on a pre- or ceCT. Contours for tumor and organs at risk (OAR) were manually constructed and copied onto both CT's; IM-SBRT plans were calculated on each CT in a manner that resulted in equal radiation fluence. The maximum and mean doses for OAR, and minimum, maximum, and mean doses for targets were compared. Data were collected from 40 dogs per anatomic site (head and neck, pelvis, and limbs). The average dose difference between minimum, maximum, and mean doses as calculated on pre- and ceCT plans for the gross tumor volume was less than 1% for all anatomic sites. Similarly, the differences between mean and maximum doses for OAR were less than 1%. The difference in dose distribution between plans made on CTs with and without contrast enhancement was tolerable at all treatment sites. Therefore, although caution would be recommended when planning IM-SBRT for tumors near "reservoirs" for contrast media (such as the heart and urinary bladder), findings supported the use of ceCT with this dose calculation algorithm for both target delineation and IM-SBRT treatment planning. © 2015 American College of Veterinary Radiology.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Osterwald, C. R.; Anderberg, A.; Rummel, S.

We present an analysis of the results of a solar weathering program that found a linear relationship between maximum power degradation and the total UV exposure dose for four different types of commercial crystalline Si modules. The average degradation rate for the four modules types was 0.71% per year. The analysis showed that losses of short-circuit current were responsible for the maximum power degradation. Judging by the appearance of the undegraded control modules, it is very doubtful that the short-circuit current losses were caused by encapsulation browning or obscuration. When we compared the quantum efficiency of a single cell inmore » a degraded module to one from an unexposed control module, it appears that most of the degradation has occurred in the 800 - 1100 nm wave-length region, and not the short wavelength region.« less

Comparative single-dose pharmacokinetics of clonazepam following intravenous, intramuscular and oral administration to healthy volunteers.

PubMed

Crevoisier, C; Delisle, M C; Joseph, I; Foletti, G

2003-01-01

The objective was to assess the single-dose pharmacokinetics of clonazepam following i.m., p.o. and i.v. administration. In an open-label, three-way crossover study, 12 healthy volunteers were randomized to receive a single dose of 2 mg clonazepam either by the i.m., p.o. or i.v. route. Serial blood samples were collected up to 120 h after drug administration. Plasma concentrations of clonazepam were determined by electron-capture gas-liquid chromatography. The absorption rates of clonazepam after i.m. and p.o. administration of clonazepam were significantly different from each other, as reflected by the respective mean values of maximum plasma concentration (C(max) 11.0 vs. 14.9 ng.ml(-1)) and time to reach maximum concentration (t(max) 3.1 vs. 1.7 h). Secondary plasma peaks of clonazepam were observed in 9 volunteers after i.m. injection (C(max) 9.9 ng.ml(-1); t(max) 10.4 h). A comparison of the area under the plasma concentration-time curves (AUC) shows that the i.m. route is equivalent to the oral route (AUC(0- infinity ) 620 vs. 561 ng.h.ml(-1)). Clonazepam was almost completely absorbed after i.m. and p.o. administration, as shown by the mean absolute bioavailability of 93 and 90%, respectively. No significant differences existed between the elimination half-lives (i.v. 38.0 h; i.m. 43.6 h; p.o. 39.0 h). The average clearance and volume of distribution (V(Z)) were 55 ml.min(-1) and 180 liters, respectively. In conclusion, the observed differences in C(max) and t(max) after i.m. and p.o. administration were consistent with a slower absorption rate of clonazepam after i.m. injection. The systemic exposure to clonazepam was not affected by the route of extravascular administration. Statistical evaluation of these kinetic data showed differences in the absorption rate, so that clonazepam given by the i.m. route is not bioequivalent to the oral route. On the basis of the results of this study, we would recommend the same i.m. and p.o. dose in epileptic patients, but therapeutic response would be expected to be less predictable and to occur later in the case of i.m. administration. Copyright 2003 S. Karger AG, Basel

Dosimetric evaluation of synthetic CT for magnetic resonance-only based radiotherapy planning of lung cancer.

PubMed

Wang, Hesheng; Chandarana, Hersh; Block, Kai Tobias; Vahle, Thomas; Fenchel, Matthias; Das, Indra J

2017-06-26

Interest in MR-only treatment planning for radiation therapy is growing rapidly with the emergence of integrated MRI/linear accelerator technology. The purpose of this study was to evaluate the feasibility of using synthetic CT images generated from conventional Dixon-based MRI scans for radiation treatment planning of lung cancer. Eleven patients who underwent whole-body PET/MR imaging following a PET/CT exam were randomly selected from an ongoing prospective IRB-approved study. Attenuation maps derived from the Dixon MR Images and atlas-based method was used to create CT data (synCT). Treatment planning for radiation treatment of lung cancer was optimized on the synCT and subsequently copied to the registered CT (planCT) for dose calculation. Planning target volumes (PTVs) with three sizes and four different locations in the lung were planned for irradiation. The dose-volume metrics comparison and 3D gamma analysis were performed to assess agreement between the synCT and CT calculated dose distributions. Mean differences between PTV doses on synCT and CT across all the plans were -0.1% ± 0.4%, 0.1% ± 0.5%, and 0.4% ± 0.5% for D95, D98 and D100, respectively. Difference in dose between the two datasets for organs at risk (OARs) had average differences of -0.14 ± 0.07 Gy, 0.0% ± 0.1%, and -0.1% ± 0.2% for maximum spinal cord, lung V20, and heart V40 respectively. In patient groups based on tumor size and location, no significant differences were observed in the PTV and OARs dose-volume metrics (p > 0.05), except for the maximum spinal-cord dose when the target volumes were located at the lung apex (p = 0.001). Gamma analysis revealed a pass rate of 99.3% ± 1.1% for 2%/2 mm (dose difference/distance to agreement) acceptance criteria in every plan. The synCT generated from Dixon-based MRI allows for dose calculation of comparable accuracy to the standard CT for lung cancer treatment planning. The dosimetric agreement between synCT and CT calculated doses warrants further development of a MR-only workflow for radiotherapy of lung cancer.

Novel, full 3D scintillation dosimetry using a static plenoptic camera.

PubMed

Goulet, Mathieu; Rilling, Madison; Gingras, Luc; Beddar, Sam; Beaulieu, Luc; Archambault, Louis

2014-08-01

Patient-specific quality assurance (QA) of dynamic radiotherapy delivery would gain from being performed using a 3D dosimeter. However, 3D dosimeters, such as gels, have many disadvantages limiting to quality assurance, such as tedious read-out procedures and poor reproducibility. The purpose of this work is to develop and validate a novel type of high resolution 3D dosimeter based on the real-time light acquisition of a plastic scintillator volume using a plenoptic camera. This dosimeter would allow for the QA of dynamic radiation therapy techniques such as intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT). A Raytrix R5 plenoptic camera was used to image a 10 × 10 × 10 cm(3) EJ-260 plastic scintillator embedded inside an acrylic phantom at a rate of one acquisition per second. The scintillator volume was irradiated with both an IMRT and VMAT treatment plan on a Clinac iX linear accelerator. The 3D light distribution emitted by the scintillator volume was reconstructed at a 2 mm resolution in all dimensions by back-projecting the light collected by each pixel of the light-field camera using an iterative reconstruction algorithm. The latter was constrained by a beam's eye view projection of the incident dose acquired using the portal imager integrated with the linac and by physical consideration of the dose behavior as a function of depth in the phantom. The absolute dose difference between the reconstructed 3D dose and the expected dose calculated using the treatment planning software Pinnacle(3) was on average below 1.5% of the maximum dose for both integrated IMRT and VMAT deliveries, and below 3% for each individual IMRT incidences. Dose agreement between the reconstructed 3D dose and a radiochromic film acquisition in the same experimental phantom was on average within 2.1% and 1.2% of the maximum recorded dose for the IMRT and VMAT delivery, respectively. Using plenoptic camera technology, the authors were able to perform millimeter resolution, water-equivalent dosimetry of an IMRT and VMAT plan over a whole 3D volume. Since no moving parts are required in the dosimeter, the incident dose distribution can be acquired as a function of time, thus enabling the validation of static and dynamic radiation delivery with photons, electrons, and heavier ions.

Novel, full 3D scintillation dosimetry using a static plenoptic camera

PubMed Central

Goulet, Mathieu; Rilling, Madison; Gingras, Luc; Beddar, Sam; Beaulieu, Luc; Archambault, Louis

2014-01-01

Purpose: Patient-specific quality assurance (QA) of dynamic radiotherapy delivery would gain from being performed using a 3D dosimeter. However, 3D dosimeters, such as gels, have many disadvantages limiting to quality assurance, such as tedious read-out procedures and poor reproducibility. The purpose of this work is to develop and validate a novel type of high resolution 3D dosimeter based on the real-time light acquisition of a plastic scintillator volume using a plenoptic camera. This dosimeter would allow for the QA of dynamic radiation therapy techniques such as intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT). Methods: A Raytrix R5 plenoptic camera was used to image a 10 × 10 × 10 cm3 EJ-260 plastic scintillator embedded inside an acrylic phantom at a rate of one acquisition per second. The scintillator volume was irradiated with both an IMRT and VMAT treatment plan on a Clinac iX linear accelerator. The 3D light distribution emitted by the scintillator volume was reconstructed at a 2 mm resolution in all dimensions by back-projecting the light collected by each pixel of the light-field camera using an iterative reconstruction algorithm. The latter was constrained by a beam's eye view projection of the incident dose acquired using the portal imager integrated with the linac and by physical consideration of the dose behavior as a function of depth in the phantom. Results: The absolute dose difference between the reconstructed 3D dose and the expected dose calculated using the treatment planning software Pinnacle3 was on average below 1.5% of the maximum dose for both integrated IMRT and VMAT deliveries, and below 3% for each individual IMRT incidences. Dose agreement between the reconstructed 3D dose and a radiochromic film acquisition in the same experimental phantom was on average within 2.1% and 1.2% of the maximum recorded dose for the IMRT and VMAT delivery, respectively. Conclusions: Using plenoptic camera technology, the authors were able to perform millimeter resolution, water-equivalent dosimetry of an IMRT and VMAT plan over a whole 3D volume. Since no moving parts are required in the dosimeter, the incident dose distribution can be acquired as a function of time, thus enabling the validation of static and dynamic radiation delivery with photons, electrons, and heavier ions. PMID:25086549

Efficacy of vincristine and etoposide with escalating cyclophosphamide in poor-prognosis pediatric brain tumors1

PubMed Central

Ziegler, David S.; Cohn, Richard J.; McCowage, Geoffrey; Alvaro, Frank; Oswald, Cecilia; Mrongovius, Robert; White, Les

2006-01-01

The objective of this study was to assess the efficacy of the VETOPEC regimen, a regimen of vincristine and etoposide with escalating doses of cyclophosphamide (CPA), in pediatric patients with high-risk brain tumors. Three consecutive studies by the Australia and New Zealand Children’s Cancer Study Group—VETOPEC I, Baby Brain 91, and VETOPEC II—have used a specific chemotherapy regimen of vincristine (VCR), etoposide (VP-16) and escalating CPA in patients with relapsed, refractory, or high-risk solid tumors. Patients in the VETOPEC II cohort were treated with very high dose CPA with peripheral blood stem cell (PBSC) rescue. We analyzed the subset of patients with high-risk brain tumors treated with these intensive VETOPEC-based protocols to assess the response, toxicity, and survival. We also assessed whether the use of very high dose chemotherapy with stem cell rescue improved the response rate or affected toxicity. Seventy-one brain tumor patients were treated with VETOPEC-based protocols. Of the 54 patients evaluable for tumor response, 17 had a complete response (CR) and 20 a partial response (PR) to treatment, which yielded an overall response rate of 69%. The CR + PR was 83% (19/23) for medulloblastomas, 56% (5/9) for primitive neuroectodermal tumors, 55% (6/11) for grade 3 and 4 astrocytomas, and 80% (6/8) for ependymomas. At a median follow-up of 36 months, overall survival for the entire cohort of 71 patients was 32%, with event-free survival of 13%. There were no toxic deaths within the PBSC-supported VETOPEC II cohort, despite higher CPA doses, compared with 7% among the non-PBSC patients. This regimen produces high response rates in a variety of very poor prognosis pediatric brain tumors. The maximum tolerated dose of CPA was not reached. Higher escalation in doses of CPA did not deliver a further improvement in response. With PBSC rescue in the VETOPEC II study, hematologic toxicity was no longer a limiting factor. The response rates observed support further development of this chemotherapy regimen. PMID:16443948

Characterization of a novel two dimensional diode array the "magic plate" as a radiation detector for radiation therapy treatment.

PubMed

Wong, J H D; Fuduli, I; Carolan, M; Petasecca, M; Lerch, M L F; Perevertaylo, V L; Metcalfe, P; Rosenfeld, A B

2012-05-01

Intensity modulated radiation therapy (IMRT) utilizes the technology of multileaf collimators to deliver highly modulated and complex radiation treatment. Dosimetric verification of the IMRT treatment requires the verification of the delivered dose distribution. Two dimensional ion chamber or diode arrays are gaining popularity as a dosimeter of choice due to their real time feedback compared to film dosimetry. This paper describes the characterization of a novel 2D diode array, which has been named the "magic plate" (MP). It was designed to function as a 2D transmission detector as well as a planar detector for dose distribution measurements in a solid water phantom for the dosimetric verification of IMRT treatment delivery. The prototype MP is an 11 × 11 detector array based on thin (50 μm) epitaxial diode technology mounted on a 0.6 mm thick Kapton substrate using a proprietary "drop-in" technology developed by the Centre for Medical Radiation Physics, University of Wollongong. A full characterization of the detector was performed, including radiation damage study, dose per pulse effect, percent depth dose comparison with CC13 ion chamber and build up characteristics with a parallel plane ion chamber measurements, dose linearity, energy response and angular response. Postirradiated magic plate diodes showed a reproducibility of 2.1%. The MP dose per pulse response decreased at higher dose rates while at lower dose rates the MP appears to be dose rate independent. The depth dose measurement of the MP agrees with ion chamber depth dose measurements to within 0.7% while dose linearity was excellent. MP showed angular response dependency due to the anisotropy of the silicon diode with the maximum variation in angular response of 10.8% at gantry angle 180°. Angular dependence was within 3.5% for the gantry angles ± 75°. The field size dependence of the MP at isocenter agrees with ion chamber measurement to within 1.1%. In the beam perturbation study, the surface dose increased by 12.1% for a 30 × 30 cm(2) field size at the source to detector distance (SDD) of 80 cm whilst the transmission for the MP was 99%. The radiation response of the magic plate was successfully characterized. The array of epitaxial silicon based detectors with "drop-in" packaging showed properties suitable to be used as a simplified multipurpose and nonperturbing 2D radiation detector for radiation therapy dosimetric verification.

Dosimetry in differentiated thyroid carcinoma (12-1402R)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Minguez, Pablo; Genolla, Jose; Celeiro, Jose Javier

2013-01-15

Purpose: The aim of this study has been to perform a dosimetric study in the treatments of differentiated thyroid cancer (DTC) performed in our center in order to find a dose-effect correlation. Methods: Thirty patients treated for DTC with 3700 MBq of {sup 131}I have been included in this study. For reasons of radiological protection all of them spent two nights as inpatients. Dose rate at 1 m from all patients was measured approximately 20 and 44 h after the administration of the radioiodine and a whole body scan in the gamma camera was performed approximately 1 week later. Withmore » those measurements and by using a model of two compartments the activities in thyroid bed remnants and in the whole body were calculated as a function of time. The integration of both activities yields the corresponding cumulated activities. Absorbed doses to thyroid bed remnants and to the whole body can be calculated following the MIRDOSE method-that is, by multiplying the corresponding cumulated activities by the corresponding S factors. Results: The absorbed doses to thyroid bed remnants calculated in this study fall into a very wide range (13-1161 Gy) and showed the highest correlation factors with the following parameters: the absorbed dose rate to thyroid bed remnants, the cumulated activity in thyroid bed remnants, and the maximum radioiodine uptake in thyroid bed remnants. The absorbed doses to the whole body range from 0.12 to 0.23 Gy. The ablation was successful in all patients, and in spite of the wide range of absorbed doses to thyroid bed remnants obtained, no dose-effect correlation could be obtained. Conclusions: Facing DTC treatments from a dosimetric viewpoint in which a predosimetry to calculate the activity of {sup 131}I to be administered is performed is a subject difficult to handle. This statement is based on the fact that although a very wide range of absorbed doses to thyroid bed remnants was obtained (including several absorbed doses well below some dose thresholds previously published to achieve ablation of thyroid bed remnants), ablation of thyroid bed remnants was successful for all patients and therefore no dose-effect correlation could be determined.« less

Applications of tissue heterogeneity corrections and biologically effective dose volume histograms in assessing the doses for accelerated partial breast irradiation using an electronic brachytherapy source.

PubMed

Shi, Chengyu; Guo, Bingqi; Cheng, Chih-Yao; Eng, Tony; Papanikolaou, Nikos

2010-09-21

A low-energy electronic brachytherapy source (EBS), the model S700 Axxent x-ray device developed by Xoft Inc., has been used in high dose rate (HDR) intracavitary accelerated partial breast irradiation (APBI) as an alternative to an Ir-192 source. The prescription dose and delivery schema of the electronic brachytherapy APBI plan are the same as the Ir-192 plan. However, due to its lower mean energy than the Ir-192 source, an EBS plan has dosimetric and biological features different from an Ir-192 source plan. Current brachytherapy treatment planning methods may have large errors in treatment outcome prediction for an EBS plan. Two main factors contribute to the errors: the dosimetric influence of tissue heterogeneities and the enhancement of relative biological effectiveness (RBE) of electronic brachytherapy. This study quantified the effects of these two factors and revisited the plan quality of electronic brachytherapy APBI. The influence of tissue heterogeneities is studied by a Monte Carlo method and heterogeneous 'virtual patient' phantoms created from CT images and structure contours; the effect of RBE enhancement in the treatment outcome was estimated by biologically effective dose (BED) distribution. Ten electronic brachytherapy APBI cases were studied. The results showed that, for electronic brachytherapy cases, tissue heterogeneities and patient boundary effect decreased dose to the target and skin but increased dose to the bones. On average, the target dose coverage PTV V(100) reduced from 95.0% in water phantoms (planned) to only 66.7% in virtual patient phantoms (actual). The actual maximum dose to the ribs is 3.3 times higher than the planned dose; the actual mean dose to the ipsilateral breast and maximum dose to the skin were reduced by 22% and 17%, respectively. Combining the effect of tissue heterogeneities and RBE enhancement, BED coverage of the target was 89.9% in virtual patient phantoms with RBE enhancement (actual BED) as compared to 95.2% in water phantoms without RBE enhancement (planned BED). About 10% increase in the source output is required to raise BED PTV V(100) to 95%. As a conclusion, the composite effect of dose reduction in the target due to heterogeneities and RBE enhancement results in a net effect of 5.3% target BED coverage loss for electronic brachytherapy. Therefore, it is suggested that about 10% increase in the source output may be necessary to achieve sufficient target coverage higher than 95%.

Applications of tissue heterogeneity corrections and biologically effective dose volume histograms in assessing the doses for accelerated partial breast irradiation using an electronic brachytherapy source

NASA Astrophysics Data System (ADS)

Shi, Chengyu; Guo, Bingqi; Cheng, Chih-Yao; Eng, Tony; Papanikolaou, Nikos

2010-09-01

A low-energy electronic brachytherapy source (EBS), the model S700 Axxent™ x-ray device developed by Xoft Inc., has been used in high dose rate (HDR) intracavitary accelerated partial breast irradiation (APBI) as an alternative to an Ir-192 source. The prescription dose and delivery schema of the electronic brachytherapy APBI plan are the same as the Ir-192 plan. However, due to its lower mean energy than the Ir-192 source, an EBS plan has dosimetric and biological features different from an Ir-192 source plan. Current brachytherapy treatment planning methods may have large errors in treatment outcome prediction for an EBS plan. Two main factors contribute to the errors: the dosimetric influence of tissue heterogeneities and the enhancement of relative biological effectiveness (RBE) of electronic brachytherapy. This study quantified the effects of these two factors and revisited the plan quality of electronic brachytherapy APBI. The influence of tissue heterogeneities is studied by a Monte Carlo method and heterogeneous 'virtual patient' phantoms created from CT images and structure contours; the effect of RBE enhancement in the treatment outcome was estimated by biologically effective dose (BED) distribution. Ten electronic brachytherapy APBI cases were studied. The results showed that, for electronic brachytherapy cases, tissue heterogeneities and patient boundary effect decreased dose to the target and skin but increased dose to the bones. On average, the target dose coverage PTV V100 reduced from 95.0% in water phantoms (planned) to only 66.7% in virtual patient phantoms (actual). The actual maximum dose to the ribs is 3.3 times higher than the planned dose; the actual mean dose to the ipsilateral breast and maximum dose to the skin were reduced by 22% and 17%, respectively. Combining the effect of tissue heterogeneities and RBE enhancement, BED coverage of the target was 89.9% in virtual patient phantoms with RBE enhancement (actual BED) as compared to 95.2% in water phantoms without RBE enhancement (planned BED). About 10% increase in the source output is required to raise BED PTV V100 to 95%. As a conclusion, the composite effect of dose reduction in the target due to heterogeneities and RBE enhancement results in a net effect of 5.3% target BED coverage loss for electronic brachytherapy. Therefore, it is suggested that about 10% increase in the source output may be necessary to achieve sufficient target coverage higher than 95%.

A method to reduce patient's eye lens dose in neuro-interventional radiology procedures

NASA Astrophysics Data System (ADS)

Safari, M. J.; Wong, J. H. D.; Kadir, K. A. A.; Sani, F. M.; Ng, K. H.

2016-08-01

Complex and prolonged neuro-interventional radiology procedures using the biplane angiography system increase the patient's risk of radiation-induced cataract. Physical collimation is the most effective way of reducing the radiation dose to the patient's eye lens, but in instances where collimation is not possible, an attenuator may be useful in protecting the eyes. In this study, an eye lens protector was designed and fabricated to reduce the radiation dose to the patients' eye lens during neuro-interventional procedures. The eye protector was characterised before being tested on its effectiveness in a simulated aneurysm procedure on an anthropomorphic phantom. Effects on the automatic dose rate control (ADRC) and image quality are also evaluated. The eye protector reduced the radiation dose by up to 62.1% at the eye lens. The eye protector is faintly visible in the fluoroscopy images and increased the tube current by a maximum of 3.7%. It is completely invisible in the acquisition mode and does not interfere with the clinical procedure. The eye protector placed within the radiation field of view was able to reduce the radiation dose to the eye lens by direct radiation beam of the lateral x-ray tube with minimal effect on the ADRC system.

ESTIMATION OF EXPOSURE DOSES FOR THE SAFE MANAGEMENT OF NORM WASTE DISPOSAL.

PubMed

Jeong, Jongtae; Ko, Nak Yul; Cho, Dong-Keun; Baik, Min Hoon; Yoon, Ki-Hoon

2018-03-16

Naturally occurring radioactive materials (NORM) wastes with different radiological characteristics are generated in several industries. The appropriate options for NORM waste management including disposal options should be discussed and established based on the act and regulation guidelines. Several studies calculated the exposure dose and mass of NORM waste to be disposed in landfill site by considering the activity concentration level and exposure dose. In 2012, the Korean government promulgated an act on the safety control of NORM around living environments to protect human health and the environment. For the successful implementation of this act, we suggest a reference design for a landfill for the disposal of NORM waste. Based on this reference landfill, we estimate the maximum exposure doses and the relative impact of each pathway to exposure dose for three scenarios: a reference scenario, an ingestion pathway exclusion scenario, and a low leach rate scenario. Also, we estimate the possible quantity of NORM waste disposal into a landfill as a function of the activity concentration level of U series, Th series and 40K and two kinds of exposure dose levels, 1 and 0.3 mSv/y. The results of this study can be used to support the establishment of technical bases of the management strategy for the safe disposal of NORM waste.

Dose-response effects in an outbreak of Salmonella enteritidis.

PubMed Central

Mintz, E. D.; Cartter, M. L.; Hadler, J. L.; Wassell, J. T.; Zingeser, J. A.; Tauxe, R. V.

1994-01-01

The effects of ingested Salmonella enteritidis (SE) dose on incubation period and on the severity and duration of illness were estimated in a cohort of 169 persons who developed gastroenteritis after eating hollandaise sauce made from grade-A shell eggs. The cohort was divided into three groups based on self-reported dose of sauce ingested. As dose increased, median incubation period decreased (37 h in the low exposure group v. 21 h in the medium exposure group v. 17.5 h in the high exposure group, P = 0.006) and greater proportions reported body aches (71 v. 85 v. 94%, P = 0.0009) and vomiting (21 v. 56 v. 57%, P = 0.002). Among 118 case-persons who completed a follow-up questionnaire, increased dose was associated with increases in median weight loss in kilograms (3.2 v. 4.5 v. 5.0, P = 0.0001), maximum daily number of stools (12.5 v. 15.0 v. 20.0, P = 0.02), subjective rating of illness severity (P = 0.0007), and the number of days of confinement to bed (3.0 v. 6.5 v. 6.5, P = 0.04). In this outbreak, ingested dose was an important determinant of the incubation period, symptoms and severity of acute salmonellosis. PMID:8119352

Dose-response effects in an outbreak of Salmonella enteritidis.

PubMed

Mintz, E D; Cartter, M L; Hadler, J L; Wassell, J T; Zingeser, J A; Tauxe, R V

1994-02-01

The effects of ingested Salmonella enteritidis (SE) dose on incubation period and on the severity and duration of illness were estimated in a cohort of 169 persons who developed gastroenteritis after eating hollandaise sauce made from grade-A shell eggs. The cohort was divided into three groups based on self-reported dose of sauce ingested. As dose increased, median incubation period decreased (37 h in the low exposure group v. 21 h in the medium exposure group v. 17.5 h in the high exposure group, P = 0.006) and greater proportions reported body aches (71 v. 85 v. 94%, P = 0.0009) and vomiting (21 v. 56 v. 57%, P = 0.002). Among 118 case-persons who completed a follow-up questionnaire, increased dose was associated with increases in median weight loss in kilograms (3.2 v. 4.5 v. 5.0, P = 0.0001), maximum daily number of stools (12.5 v. 15.0 v. 20.0, P = 0.02), subjective rating of illness severity (P = 0.0007), and the number of days of confinement to bed (3.0 v. 6.5 v. 6.5, P = 0.04). In this outbreak, ingested dose was an important determinant of the incubation period, symptoms and severity of acute salmonellosis.

Phase 1 first-in-human studies of the reactogenicity and immunogenicity of a recombinant meningococcal NspA vaccine in healthy adults.

PubMed

Halperin, Scott A; Langley, Joanne M; Smith, Bruce; Wunderli, Peter; Kaufman, Lisa; Kimura, Alan; Martin, Denis

2007-01-05

Neisserial surface protein A (NspA) is a highly conserved, surface-exposed outer membrane protein of Neisseria meningitidis that has been shown to induce a bactericidal immune response in animals against all pathogenic Neisserial serogroups. Healthy 18-50-year-old adults were assigned to receive, in a dose escalating manner, 3 doses of 1 of 5 formulations of an experimental, unfolded, recombinant NspA (rNspA) vaccine or placebo, or 1 dose of commercially available quadravalent (A, C, Y, W-135) meningococcal polysaccharide vaccine (Menomune((R))). Adverse events were collected during the first week post-immunization, prior to the next dose and 1 month after the last dose. Serum for measurement of hematological and biochemical parameters and antibodies by enzyme immunoassay and bactericidal assay were measured before the first dose, prior to the second dose and 1 month after the last dose of vaccine. The rNspA vaccine was well tolerated by recipients. Injection-site pain was reported more frequently by recipients of the three highest doses of rNspA compared to placebo but at similar rates to the licensed meningococcal polysaccharide vaccine. Adverse events were reported less frequently after subsequent doses in the three-dose series. An antibody rise measured by enzyme immunoassay was elicited with a dose-related increase that reached a maximum with the 125mug dose. Prolongation of the dosing interval between the second and third dose appeared to be associated with increased antibody levels. No bactericidal antibodies were detected after any of the rNspA formulations. The unfolded rNspA meningococcal vaccine was well tolerated and immunogenic in healthy adult volunteers but did not elicit bactericidal antibodies.

Effect of gamma-ray irradiation on the dewaterability of waste activated sludge

NASA Astrophysics Data System (ADS)

Wu, Yuqi; Jiang, Yinghe; Ke, Guojun; Liu, Yingjiu

2017-01-01

The effect of gamma-ray irradiation on waste activated sludge (WAS) dewaterability was investigated with irradiation doses of 0-15 kGy. Time to filter (TTF50), specific resistance of filtration (SRF) and water content of sludge cake were measured to evaluate sludge dewaterability. Soluble chemical oxygen demand (SCOD), soluble extracellular polymeric substances (EPS) concentration and sludge particle size were determined to explain changes in sludge dewaterability. The optimal irradiation dose to obtain the maximum dewaterability characteristics was 1-4 kGy, which generated sludge with optimal disintegration (1.5-4.0%), soluble EPS concentration (590-750 mg/L) and particle size distribution (100-115 μm diameter). The combination of irradiation and cationic polyacrylamide (CPAM) addition exhibited minimal synergistic effect on increasing sludge dewatering rate compared with CPAM conditioning alone.

Volumetric tumor burden and its effect on brachial plexus dosimetry in head and neck intensity-modulated radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Romesser, Paul B.; Qureshi, Muhammad M.; Kovalchuk, Nataliya

2014-07-01

To determine the effect of gross tumor volume of the primary (GTV-P) and nodal (GTV-N) disease on planned radiation dose to the brachial plexus (BP) in head and neck intensity-modulated radiotherapy (IMRT). Overall, 75 patients underwent definitive IMRT to a median total dose of 69.96 Gy in 33 fractions. The right BP and left BP were prospectively contoured as separate organs at risk. The GTV was related to BP dose using the unpaired t-test. Receiver operating characteristics curves were constructed to determine optimized volumetric thresholds of GTV-P and GTV-N corresponding to a maximum BP dose cutoff of > 66 Gy.more » Multivariate analyses were performed to account for factors associated with a higher maximal BP dose. A higher maximum BP dose (> 66 vs ≤ 66 Gy) correlated with a greater mean GTV-P (79.5 vs 30.8 cc; p = 0.001) and ipsilateral GTV-N (60.6 vs 19.8 cc; p = 0.014). When dichotomized by the optimized nodal volume, patients with an ipsilateral GTV-N ≥ 4.9 vs < 4.9 cc had a significant difference in maximum BP dose (64.2 vs 59.4 Gy; p = 0.001). Multivariate analysis confirmed that an ipsilateral GTV-N ≥ 4.9 cc was an independent predictor for the BP to receive a maximal dose of > 66 Gy when adjusted individually for BP volume, GTV-P, the use of a low anterior neck field technique, total planned radiation dose, and tumor category. Although both the primary and the nodal tumor volumes affected the BP maximal dose, the ipsilateral nodal tumor volume (GTV-N ≥ 4.9 cc) was an independent predictor for high maximal BP dose constraints in head and neck IMRT.« less

Final Report for the Testing of the Y-12 Criticality Accident Alarm System Detectors at the Godiva IV Burst Reactor (IER-443)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scorby, John C.; Hickman, David; Hudson, Becka

This report documents the experimental conditions and final results for the performance testing of the Y-12 Criticality Accident Alarm System (CAAS) detectors at the Godiva IV Burst Reactor at the National Criticality Experimental Research Center (NCERC) at the Nevada National Security Site (NNSS). The testing followed a previously issued test plan and was conducted during the week of July 17, 2017, with completion on Thursday July 20. The test subjected CAAS detectors supplied by Y-12 to very intense and short duration mixed neutron and gamma radiation fields to establish compliance to maximum radiation and minimum pulse width requirements. ANSI/ANS- 8.3.1997more » states that the “system shall be sufficiently robust as to actuate an alarm signal when exposed to the maximum radiation expected”, which has been defined at Y-12, in Documented Safety Analyses (DSAs), to be a dose rate of 10 Rad/s. ANSI/ANS-8.3.1997 further states that “alarm actuation shall occur as a result of a minimum duration transient” which may be assumed to be 1 msec. The pulse widths and dose rates provided by each burst during the test exceeded those requirements. The CAAS detectors all provided an immediate alarm signal and remained operable after the bursts establishing compliance to the requirements and fitness for re-deployment at Y-12.« less

Stereotactic Fractionated Radiotherapy and LINAC Radiosurgery in the Treatment of Vestibular Schwannoma-Report About Both Stereotactic Methods From a Single Institution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kopp, Christine, E-mail: Christine.Kopp@lrz.tu-muenchen.de; Fauser, Claudius; Mueller, Axel

2011-08-01

Purpose: To evaluate tumor control and side effects associated with radiosurgery (RS) and stereotactic fractionated radiotherapy (SFR) for vestibular schwannomas (VSs) in a group of patients treated at the same institution. Methods and Materials: Between May 1997 and June 2007, 115 consecutive cases of VS were treated in our department. The SFR group (47 patients), including larger tumors (maximum diameter >1.5 cm), received a total dose of 54 Gy at 1.8 Gy per fraction. The RS group (68 patients, maximum diameter <1.5 cm) received a total dose of 12 Gy at the 100% isodose. Evaluation included serial imaging tests (magneticmore » resonance imaging) and neurologic and functional hearing examinations. Results: The tumor control rate was 97.9% in the SFR group for a mean follow-up time of 32.1 months and 98.5% in the RS group for a mean follow-up time of 30.1 months. Hearing function was preserved after RS in 85% of the patients and after SFR in 79%. Facial and trigeminal nerve function remained mostly unaffected after SFR. After RS, new trigeminal neuropathy occurred in 9 of 68 patients (13%). Conclusions: A high tumor control rate and low number of side effects are registered after SFR and RS of VS. These results confirm that considering tumor diameter, both RS and SFR are good treatment modalities for VS.« less

Influence of grid control and object detection on radiation exposure and image quality using mobile C-arms - first results.

PubMed

Gosch, D; Ratzmer, A; Berauer, P; Kahn, T

2007-09-01

The objective of this study was to examine the extent to which the image quality on mobile C-arms can be improved by an innovative exposure rate control system (grid control). In addition, the possible dose reduction in the pulsed fluoroscopy mode using 25 pulses/sec produced by automatic adjustment of the pulse rate through motion detection was to be determined. As opposed to conventional exposure rate control systems, which use a measuring circle in the center of the field of view, grid control is based on a fine mesh of square cells which are overlaid on the entire fluoroscopic image. The system uses only those cells for exposure control that are covered by the object to be visualized. This is intended to ensure optimally exposed images, regardless of the size, shape and position of the object to be visualized. The system also automatically detects any motion of the object. If a pulse rate of 25 pulses/sec is selected and no changes in the image are observed, the pulse rate used for pulsed fluoroscopy is gradually reduced. This may decrease the radiation exposure. The influence of grid control on image quality was examined using an anthropomorphic phantom. The dose reduction achieved with the help of object detection was determined by evaluating the examination data of 146 patients from 5 different countries. The image of the static phantom made with grid control was always optimally exposed, regardless of the position of the object to be visualized. The average dose reduction when using 25 pulses/sec resulting from object detection and automatic down-pulsing was 21 %, and the maximum dose reduction was 60 %. Grid control facilitates C-arm operation, since optimum image exposure can be obtained independently of object positioning. Object detection may lead to a reduction in radiation exposure for the patient and operating staff.

Fetal radiation dose estimates for I-131 sodium iodide in cases where conception occurs after administration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sparks, R.B.; Stabin, M.G.

1999-01-01

After administration of I-131 to the female patient, the possibility of radiation exposure of the embryo/fetus exists if the patient becomes pregnant while radioiodine remains in the body. Fetal radiation dose estimates for such cases were calculated. Doses were calculated for various maternal thyroid uptakes and time intervals between administration and conception, including euthyroid and hyperthyroid cases. The maximum fetal dose calculating was about 9.8E-03 mGy/MBq, which occurred with 100% maternal thyroid uptake and a 1 week interval between administration and conception. Placental crossover of the small amount of radioiodine remaining 90 days after conception was also considered. Such crossovermore » could result in an additional fetal dose of 9.8E-05 mGy/MBq and a maximum fetal thyroid self dose of 3.5E-04 mGy/MBq.« less

In vivo dosimetry for external photon treatments of head and neck cancers by diodes and TLDS.

PubMed

Tung, C J; Wang, H C; Lo, S H; Wu, J M; Wang, C J

2004-01-01

In vivo dosimetry was implemented for treatments of head and neck cancers in the large fields. Diode and thermoluminescence dosemeter (TLD) measurements were carried out for the linear accelerators of 6 MV photon beams. ESTRO in vivo dosimetry protocols were followed in the determination of midline doses from measurements of entrance and exit doses. Of the fields monitored by diodes, the maximum absolute deviation of measured midline doses from planned target doses was 8%, with the mean value and the standard deviation of -1.0 and 2.7%. If planned target doses were calculated using radiological water equivalent thicknesses rather than patient geometric thicknesses, the maximum absolute deviation dropped to 4%, with the mean and the standard deviation of 0.7 and 1.8%. For in vivo dosimetry monitored by TLDs, the shift in mean dose remained small but the statistical precision became poor.

Whole-remnant and maximum-voxel SPECT/CT dosimetry in {sup 131}I-NaI treatments of differentiated thyroid cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mínguez, Pablo, E-mail: pablo.minguezgabina@osakid

Purpose: To investigate the possible differences between SPECT/CT based whole-remnant and maximum-voxel dosimetry in patients receiving radio-iodine ablation treatment of differentiated thyroid cancer (DTC). Methods: Eighteen DTC patients were administered 1.11 GBq of {sup 131}I-NaI after near-total thyroidectomy and rhTSH stimulation. Two patients had two remnants, so in total dosimetry was performed for 20 sites. Three SPECT/CT scans were performed for each patient at 1, 2, and 3–7 days after administration. The activity, the remnant mass, and the maximum-voxel activity were determined from these images and from a recovery-coefficient curve derived from experimental phantom measurements. The cumulated activity was estimatedmore » using trapezoidal-exponential integration. Finally, the absorbed dose was calculated using S-values for unit-density spheres in whole-remnant dosimetry and S-values for voxels in maximum-voxel dosimetry. Results: The mean absorbed dose obtained from whole-remnant dosimetry was 40 Gy (range 2–176 Gy) and from maximum-voxel dosimetry 34 Gy (range 2–145 Gy). For any given patient, the activity concentrations for each of the three time-points were approximately the same for the two methods. The effective half-lives varied (R = 0.865), mainly due to discrepancies in estimation of the longer effective half-lives. On average, absorbed doses obtained from whole-remnant dosimetry were 1.2 ± 0.2 (1 SD) higher than for maximum-voxel dosimetry, mainly due to differences in the S-values. The method-related differences were however small in comparison to the wide range of absorbed doses obtained in patients. Conclusions: Simple and consistent procedures for SPECT/CT based whole-volume and maximum-voxel dosimetry have been described, both based on experimentally determined recovery coefficients. Generally the results from the two approaches are consistent, although there is a small, systematic difference in the absorbed dose due to differences in the S-values, and some variability due to differences in the estimated effective half-lives, especially when the effective half-life is long. Irrespective of the method used, the patient absorbed doses obtained span over two orders of magnitude.« less

CT Fluoroscopy Shielding: Decreases in Scattered Radiation for the Patient and Operator

PubMed Central

Neeman, Ziv; Dromi, Sergio A.; Sarin, Shawn; Wood, Bradford J.

2008-01-01

PURPOSE High-radiation exposure occurs during computed tomographic (CT) fluoroscopy. Patient and operator doses during thoracic and abdominal interventional procedures were studied in the present experiment, and a novel shielding device to reduce exposure to the patient and operator was evaluated. MATERIALS AND METHODS With a 16-slice CT scanner in CT fluoroscopy mode (120 kVp, 30 mA), surface dosimetry was performed on adult and pediatric phantoms. The shielding was composed of tungsten antimony in the form of a lightweight polymer sheet. Doses to the patient were measured with and without shielding for thoracic and abdominal procedures. Doses to the operator were recorded with and without phantom, gantry, and table shielding in place. Double-layer lead-free gloves were used by the operator during the procedures. RESULTS Tungsten antimony shielding adjacent to the scan plane resulted in a maximum dose reduction of 92.3% to the patient. Maximum 85.6%, 93.3%, and 85.1% dose reductions were observed for the operator’s torso, gonads, and hands, respectively. The use of double-layer lead-free gloves resulted in a maximum radiation dose reduction of 97%. CONCLUSIONS Methods to reduce exposure during CT fluoroscopy are effective and should be searched for. Significant reduction in radiation doses to the patient and operator can be accomplished with tungsten antimony shielding. PMID:17185699

Using quality of life measures in a Phase I clinical trial of noni in patients with advanced cancer to select a Phase II dose.

PubMed

Issell, Brian F; Gotay, Carolyn C; Pagano, Ian; Franke, Adrian A

2009-01-01

ABSTRACT. The purpose of this study was to determine a maximum tolerated dose of noni in cancer patients and whether an optimal quality of life-sustaining dose could be identified as an alternative way to select a dose for subsequent Phase II efficacy trials. Dose levels started at two capsules twice daily (2 g), the suggested dose for the marketed product, and were escalated by 2 g daily in cohorts of at least five patients until a maximum tolerated dose was found. Patients completed subscales of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 quality of life (physical functioning, pain, and fatigue) the brief fatigue inventory (BFI), questionnaires at baseline and at approximately 4-week intervals. Blood and urine were collected at baseline and at approximately 4-week intervals for measurement of scopoletin. Fifty-one patients were enrolled at seven dose levels. The maximum tolerated dose was six capsules four times daily (12 g). Although no dose-limiting toxicity was found, seven of eight patients at the next level (14 g), withdrew due to the challenges of ingesting so many capsules. There were dose-related differences in self-reported physical functioning and pain and fatigue control. Overall, patients taking three or four capsules four times daily experienced better outcomes than patients taking lower or higher doses. Blood and urinary scopoletin concentrations related to noni dose. We concluded that it is feasible to use quality of life measures to select a Phase II dose. Three or four capsules four times daily (6-8 g) is recommended when controlling fatigue, pain, and maintaining physical function are the efficacies of interest. Scopoletin, a bioactive component of noni fruit extract, is measurable in blood and urine following noni ingestion and can be used to study the pharmacokinetics of noni in cancer patients.

GAD65 antigen therapy in recently diagnosed type 1 diabetes mellitus.

PubMed

Ludvigsson, Johnny; Krisky, David; Casas, Rosaura; Battelino, Tadej; Castaño, Luis; Greening, James; Kordonouri, Olga; Otonkoski, Timo; Pozzilli, Paolo; Robert, Jean-Jacques; Veeze, Henk J; Palmer, Jerry; Samuelsson, Ulf; Elding Larsson, Helena; Åman, Jan; Kärdell, Gunilla; Neiderud Helsingborg, Jan; Lundström, Göran; Albinsson, Eva; Carlsson, Annelie; Nordvall, Maria; Fors, Hans; Arvidsson, Carl-Göran; Edvardson, Stig; Hanås, Ragnar; Larsson, Karin; Rathsman, Björn; Forsgren, Henrik; Desaix, Helena; Forsander, Gun; Nilsson, Nils-Östen; Åkesson, Carl-Göran; Keskinen, Päivi; Veijola, Riitta; Talvitie, Timo; Raile, Klemens; Kapellen, Thomas; Burger, Walter; Neu, Andreas; Engelsberger, Ilse; Heidtmann, Bettina; Bechtold, Suzanne; Leslie, David; Chiarelli, Francesco; Cicognani, Alesandro; Chiumello, Giuseppe; Cerutti, Franco; Zuccotti, Gian Vincenzo; Gomez Gila, Ana; Rica, Itxaso; Barrio, Raquel; Clemente, Maria; López Garcia, Maria José; Rodriguez, Mercedes; Gonzalez, Isabel; Lopez, Juan Pedro; Oyarzabal, Mirentxu; Reeser, H M; Nuboer, Roos; Stouthart, Pauline; Bratina, Natasa; Bratanic, Nina; de Kerdanet, Marc; Weill, Jacques; Ser, Nicole; Barat, Pascal; Bertrand, Anne Marie; Carel, Jean-Claude; Reynaud, Rachel; Coutant, Regis; Baron, Sabine

2012-02-02

The 65-kD isoform of glutamic acid decarboxylase (GAD65) is a major autoantigen in type 1 diabetes. We hypothesized that alum-formulated GAD65 (GAD-alum) can preserve beta-cell function in patients with recent-onset type 1 diabetes. We studied 334 patients, 10 to 20 years of age, with type 1 diabetes, fasting C-peptide levels of more than 0.3 ng per milliliter (0.1 nmol per liter), and detectable serum GAD65 autoantibodies. Within 3 months after diagnosis, patients were randomly assigned to receive one of three study treatments: four doses of GAD-alum, two doses of GAD-alum followed by two doses of placebo, or four doses of placebo. The primary outcome was the change in the stimulated serum C-peptide level (after a mixed-meal tolerance test) between the baseline visit and the 15-month visit. Secondary outcomes included the glycated hemoglobin level, mean daily insulin dose, rate of hypoglycemia, and fasting and maximum stimulated C-peptide levels. The stimulated C-peptide level declined to a similar degree in all study groups, and the primary outcome at 15 months did not differ significantly between the combined active-drug groups and the placebo group (P=0.10). The use of GAD-alum as compared with placebo did not affect the insulin dose, glycated hemoglobin level, or hypoglycemia rate. Adverse events were infrequent and mild in the three groups, with no significant differences. Treatment with GAD-alum did not significantly reduce the loss of stimulated C peptide or improve clinical outcomes over a 15-month period. (Funded by Diamyd Medical and the Swedish Child Diabetes Foundation; ClinicalTrials.gov number, NCT00723411.).

SU-G-201-08: Energy Response of Thermoluminescent Microcube Dosimeters in Water for Kilovoltage X-Ray Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Di Maso, L; Lawless, M; Culberson, W

Purpose: To characterize the energy dependence for TLD-100 microcubes in water at kilovoltage energies. Methods: TLD-100 microcubes with dimensions of (1 × 1 × 1) mm{sup 3} were irradiated with kilovoltage x-rays in a custom-built thin-window liquid water phantom. The TLD-100 microcubes were held in Virtual Water™ probes and aligned at a 2 cm depth in water. Irradiations were performed using the M-series x-ray beams of energies ranging from 50-250 kVp and normalized to a {sup 60}Co beam located at the UWADCL. Simulations using the EGSnrc Monte Carlo Code System were performed to model the x-ray beams, the {sup 60}Comore » beam, the water phantom and the dosimeters in the phantom. The egs-chamber user code was used to tally the dose to the TLDs and the dose to water. The measurements and calculations were used to determine the intrinsic energy dependence, absorbed-dose energy dependence, and absorbed-dose sensitivity. These values were compared to TLD-100 chips with dimensions of (3.2 × 0.9 × 0.9) mm{sup 3}. Results: The measured TLD-100 microcube response per dose to water among all investigated x-ray energies had a maximum percent difference of 61% relative to {sup 60}Co. The simulated ratio of dose to water to the dose to TLD had a maximum percent difference of 29% relative to {sup 60}Co. The ratio of dose to TLD to the TLD output had a maximum percent difference of 13% relative to {sup 60}Co. The maximum percent difference for the absorbed-dose sensitivity was 15% more than the used value of 1.41. Conclusion: These results confirm that differences in beam quality have a significant effect on TLD response when irradiated in water. These results also indicated a difference in TLD-100 response between microcube and chip geometries. The intrinsic energy dependence and the absorbed-dose energy dependence deviated up to 10% between TLD-100 microcubes and chips.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lafata, K; Ren, L; Wu, Q

Purpose: To develop a data-mining methodology based on quantum clustering and machine learning to predict expected dosimetric endpoints for lung SBRT applications based on patient-specific anatomic features. Methods: Ninety-three patients who received lung SBRT at our clinic from 2011–2013 were retrospectively identified. Planning information was acquired for each patient, from which various features were extracted using in-house semi-automatic software. Anatomic features included tumor-to-OAR distances, tumor location, total-lung-volume, GTV and ITV. Dosimetric endpoints were adopted from RTOG-0195 recommendations, and consisted of various OAR-specific partial-volume doses and maximum point-doses. First, PCA analysis and unsupervised quantum-clustering was used to explore the feature-space tomore » identify potentially strong classifiers. Secondly, a multi-class logistic regression algorithm was developed and trained to predict dose-volume endpoints based on patient-specific anatomic features. Classes were defined by discretizing the dose-volume data, and the feature-space was zero-mean normalized. Fitting parameters were determined by minimizing a regularized cost function, and optimization was performed via gradient descent. As a pilot study, the model was tested on two esophageal dosimetric planning endpoints (maximum point-dose, dose-to-5cc), and its generalizability was evaluated with leave-one-out cross-validation. Results: Quantum-Clustering demonstrated a strong separation of feature-space at 15Gy across the first-and-second Principle Components of the data when the dosimetric endpoints were retrospectively identified. Maximum point dose prediction to the esophagus demonstrated a cross-validation accuracy of 87%, and the maximum dose to 5cc demonstrated a respective value of 79%. The largest optimized weighting factor was placed on GTV-to-esophagus distance (a factor of 10 greater than the second largest weighting factor), indicating an intuitively strong correlation between this feature and both endpoints. Conclusion: This pilot study shows that it is feasible to predict dose-volume endpoints based on patient-specific anatomic features. The developed methodology can potentially help to identify patients at risk for higher OAR doses, thus improving the efficiency of treatment planning. R01-184173.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, J; Kim, J; Park, S

Purpose: To investigate exposure outside the treatment field when treating breast cancer with tri-Co-60 magnetic resonance (MR) image guided radiation therapy (IGRT) system. Methods: A total of 7 patients who treated with accelerated partial breast irradiation (APBI) technique were selected prospectively for this study (prescription dose = 38.5 Gy in 10 fractions). Every patient treated with two plans, one was an initial plan and the other was an adaptive plan generated after finishing 5 fractions (a total of 14 plans). Every plan was calculated with and without magnetic field in the treatment planning system. The EBT3 films were attached onmore » the front and the back of 1 cm bolus, and then it was placed on the patient body vertically to cover patient’s jaw and shoulder. After measurements, the maximum point dose and the mean dose of whole area of EBT3 film were acquired. Results: In the treatment plan with magnetic field, low dose stream outside the patient body was observed, almost reaching the patient’s jaw or shoulder, while it was not observed without magnetic field. The average values of the measured maximum and mean doses at the front of bolus were 30.1 ± 11.1 cGy (7.8% of the daily dose) and 14.7 ± 3.3 cGy (3.8%), respectively. At the back of bolus, those values were 6.0 ± 1.9 cGy (1.6%) and 5.1 ± 1.6 cGy (1.3%), respectively. The largest maximum dose at the front was 54.2 cGy (14.1%) while it was 20.7 cGy (5.4%) at the back. The average decrease of the maximum dose by the bolus was 24.0 ± 11.0 cGy. Conclusion: Due to magnetic field, dose stream outside the patient body can be generated during breast cancer treatment with the tri-Co-60 MR-IGRT system. Since this dose stream irradiated skin outside the treatment field, it should be shielded. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2015R1C1A1A01054192).« less

Prediction of Normal Organ Absorbed Doses for [177Lu]Lu-PSMA-617 Using [44Sc]Sc-PSMA-617 Pharmacokinetics in Patients With Metastatic Castration Resistant Prostate Carcinoma.

PubMed

Khawar, Ambreen; Eppard, Elisabeth; Sinnes, Jean Phlippe; Roesch, Frank; Ahmadzadehfar, Hojjat; Kürpig, Stefan; Meisenheimer, Michael; Gaertner, Florian C; Essler, Markus; Bundschuh, Ralph A

2018-04-23

In vivo pharmacokinetic analysis of [Sc]Sc-PSMA-617 was used to determine the normal organ-absorbed doses that may result from therapeutic activity of [Lu]Lu-PSMA-617 and to predict the maximum permissible activity of [Lu]Lu-PSMA-617 for patients with metastatic castration-resistant prostate carcinoma. Pharmacokinetics of [Sc]Sc-PSMA-617 was evaluated in 5 patients with metastatic castration-resistant prostate carcinoma using dynamic PET/CT, followed by 3 static PET/CT acquisitions and blood sample collection over 19.5 hours, as well as urine sample collection at 2 time points. Total activity measured in source organs by PET imaging, as well as counts per milliliter measured in blood and urine samples, was decay corrected back to the time of injection using the half-life of Sc. Afterward, forward decay correction using the half-life of Lu was performed, extrapolating the pharmacokinetics of [Sc]Sc-PSMA-617 to that of [Lu]Lu-PSMA-617. Source organs residence times and organ-absorbed doses for [Lu]Lu-PSMA-617 were calculated using OLINDA/EXM software. Bone marrow self-dose was determined with indirect blood-based method, and urinary bladder contents residence time was estimated by trapezoidal approximation. The maximum permissible activity of [Lu]Lu-PSMA-617 was calculated for each patient considering external beam radiotherapy toxicity limits for radiation absorbed doses to kidneys, bone marrow, salivary glands, and whole body. The predicted mean organ-absorbed doses were highest in the kidneys (0.44 mSv/MBq), followed by the salivary glands (0.23 mSv/MBq). The maximum permissible activity was highly variable among patients; limited by whole body-absorbed dose (1 patient), marrow-absorbed dose (1 patient), and kidney-absorbed dose (3 patients). [Sc]Sc-PSMA-617 PET/CT imaging is feasible and allows theoretical extrapolation of the pharmacokinetics of [Sc]Sc-PSMA-617 to that of [Lu]Lu-PSMA-617, with the intent of predicting normal organ-absorbed doses and maximum permissible activity in patients scheduled for therapy with [Lu]Lu-PSMA-617.

Mechanistic simulation of normal-tissue damage in radiotherapy—implications for dose-volume analyses

NASA Astrophysics Data System (ADS)

Rutkowska, Eva; Baker, Colin; Nahum, Alan

2010-04-01

A radiobiologically based 3D model of normal tissue has been developed in which complications are generated when 'irradiated'. The aim is to provide insight into the connection between dose-distribution characteristics, different organ architectures and complication rates beyond that obtainable with simple DVH-based analytical NTCP models. In this model the organ consists of a large number of functional subunits (FSUs), populated by stem cells which are killed according to the LQ model. A complication is triggered if the density of FSUs in any 'critical functioning volume' (CFV) falls below some threshold. The (fractional) CFV determines the organ architecture and can be varied continuously from small (series-like behaviour) to large (parallel-like). A key feature of the model is its ability to account for the spatial dependence of dose distributions. Simulations were carried out to investigate correlations between dose-volume parameters and the incidence of 'complications' using different pseudo-clinical dose distributions. Correlations between dose-volume parameters and outcome depended on characteristics of the dose distributions and on organ architecture. As anticipated, the mean dose and V20 correlated most strongly with outcome for a parallel organ, and the maximum dose for a serial organ. Interestingly better correlation was obtained between the 3D computer model and the LKB model with dose distributions typical for serial organs than with those typical for parallel organs. This work links the results of dose-volume analyses to dataset characteristics typical for serial and parallel organs and it may help investigators interpret the results from clinical studies.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Persson, Mats, E-mail: mats.persson@mi.physics.kth

Purpose: The highest photon fluence rate that a computed tomography (CT) detector must be able to measure is an important parameter. The authors calculate the maximum transmitted fluence rate in a commercial CT scanner as a function of patient size for standard head, chest, and abdomen protocols. Methods: The authors scanned an anthropomorphic phantom (Kyoto Kagaku PBU-60) with the reference CT protocols provided by AAPM on a GE LightSpeed VCT scanner and noted the tube current applied with the tube current modulation (TCM) system. By rescaling this tube current using published measurements on the tube current modulation of a GEmore » scanner [N. Keat, “CT scanner automatic exposure control systems,” MHRA Evaluation Report 05016, ImPACT, London, UK, 2005], the authors could estimate the tube current that these protocols would have resulted in for other patient sizes. An ECG gated chest protocol was also simulated. Using measured dose rate profiles along the bowtie filters, the authors simulated imaging of anonymized patient images with a range of sizes on a GE VCT scanner and calculated the maximum transmitted fluence rate. In addition, the 99th and the 95th percentiles of the transmitted fluence rate distribution behind the patient are calculated and the effect of omitting projection lines passing just below the skin line is investigated. Results: The highest transmitted fluence rates on the detector for the AAPM reference protocols with centered patients are found for head images and for intermediate-sized chest images, both with a maximum of 3.4 ⋅ 10{sup 8} mm{sup −2} s{sup −1}, at 949 mm distance from the source. Miscentering the head by 50 mm downward increases the maximum transmitted fluence rate to 5.7 ⋅ 10{sup 8} mm{sup −2} s{sup −1}. The ECG gated chest protocol gives fluence rates up to 2.3 ⋅ 10{sup 8} − 3.6 ⋅ 10{sup 8} mm{sup −2} s{sup −1} depending on miscentering. Conclusions: The fluence rate on a CT detector reaches 3 ⋅ 10{sup 8} − 6 ⋅ 10{sup 8} mm{sup −2} s{sup −1} in standard imaging protocols, with the highest rates occurring for ECG gated chest and miscentered head scans. These results will be useful to developers of CT detectors, in particular photon counting detectors.« less

Rate of degradation of lambda-cyhalothrin and methomyl in grapes (Vitis vinifera L.).

PubMed

Banerjee, Kaushik; Upadhyay, Ajay Kumar; Adsule, Pandurang G; Patil, Sangram H; Oulkar, Dasharath P; Jadhav, Deepak R

2006-10-01

Rates of degradation of lambda-cyhalothrin and methomyl residues in grape are reported. The dissipation behavior of both insecticides followed first-order rate kinetics with similar patterns at standard and double-dose applications. Residues of lambda-cyhalothrin were lost with pre-harvest intervals (PHI) of 12.0-12.5 and 15.0-15.5 days, corresponding to the applications at 25 and 50 g a.i. ha-1, respectively. In the case of methomyl, residues were lost with PHI of 55.0 and 61.0 days, following applications at 1 and 2 kg a.i. ha-1, respectively. The PHI, recommended on the basis of the experimental results, was shown to be effective in minimizing residue load of these insecticides below their maximum residue limits (MRLs) in vineyard samples.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bosarge, Christina L., E-mail: cbosarge@umail.iu.edu; Ewing, Marvene M.; DesRosiers, Colleen M.

To demonstrate the dosimetric advantages and disadvantages of standard anteroposterior-posteroanterior (S-AP/PA{sub AAA}), inverse-planned AP/PA (IP-AP/PA) and volumetry-modulated arc (VMAT) radiotherapies in the treatment of children undergoing whole-lung irradiation. Each technique was evaluated by means of target coverage and normal tissue sparing, including data regarding low doses. A historical approach with and without tissue heterogeneity corrections is also demonstrated. Computed tomography (CT) scans of 10 children scanned from the neck to the reproductive organs were used. For each scan, 6 plans were created: (1) S-AP/PA{sub AAA} using the anisotropic analytical algorithm (AAA), (2) IP-AP/PA, (3) VMAT, (4) S-AP/PA{sub NONE} without heterogeneitymore » corrections, (5) S-AP/PA{sub PB} using the Pencil-Beam algorithm and enforcing monitor units from technique 4, and (6) S-AP/PA{sub AAA[FM]} using AAA and forcing fixed monitor units. The first 3 plans compare modern methods and were evaluated based on target coverage and normal tissue sparing. Body maximum and lower body doses (50% and 30%) were also analyzed. Plans 4 to 6 provide a historic view on the progression of heterogeneity algorithms and elucidate what was actually delivered in the past. Averages of each comparison parameter were calculated for all techniques. The S-AP/PA{sub AAA} technique resulted in superior target coverage but had the highest maximum dose to every normal tissue structure. The IP-AP/PA technique provided the lowest dose to the esophagus, stomach, and lower body doses. VMAT excelled at body maximum dose and maximum doses to the heart, spine, and spleen, but resulted in the highest dose in the 30% body range. It was, however, superior to the S-AP/PA{sub AAA} approach in the 50% range. Each approach has strengths and weaknesses thus associated. Techniques may be selected on a case-by-case basis and by physician preference of target coverage vs normal tissue sparing.« less

SU-E-T-578: On Definition of Minimum and Maximum Dose for Target Volume

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gong, Y; Yu, J; Xiao, Y

Purpose: This study aims to investigate the impact of different minimum and maximum dose definitions in radiotherapy treatment plan quality evaluation criteria by using tumor control probability (TCP) models. Methods: Dosimetric criteria used in RTOG 1308 protocol are used in the investigation. RTOG 1308 is a phase III randomized trial comparing overall survival after photon versus proton chemoradiotherapy for inoperable stage II-IIIB NSCLC. The prescription dose for planning target volume (PTV) is 70Gy. Maximum dose (Dmax) should not exceed 84Gy and minimum dose (Dmin) should not go below 59.5Gy in order for the plan to be “per protocol” (satisfactory).A mathematicalmore » model that simulates the characteristics of PTV dose volume histogram (DVH) curve with normalized volume is built. The Dmax and Dmin are noted as percentage volumes Dη% and D(100-δ)%, with η and d ranging from 0 to 3.5. The model includes three straight line sections and goes through four points: D95%= 70Gy, Dη%= 84Gy, D(100-δ)%= 59.5 Gy, and D100%= 0Gy. For each set of η and δ, the TCP value is calculated using the inhomogeneously irradiated tumor logistic model with D50= 74.5Gy and γ50=3.52. Results: TCP varies within 0.9% with η; and δ values between 0 and 1. With η and η varies between 0 and 2, TCP change was up to 2.4%. With η and δ variations from 0 to 3.5, maximum of 8.3% TCP difference is seen. Conclusion: When defined maximum and minimum volume varied more than 2%, significant TCP variations were seen. It is recommended less than 2% volume used in definition of Dmax or Dmin for target dosimetric evaluation criteria. This project was supported by NIH grants U10CA180868, U10CA180822, U24CA180803, U24CA12014 and PA CURE Grant.« less

Evaluation of Gafchromic EBT-XD film, with comparison to EBT3 film, and application in high dose radiotherapy verification.

PubMed

Palmer, Antony L; Dimitriadis, Alexis; Nisbet, Andrew; Clark, Catharine H

2015-11-21

There is renewed interest in film dosimetry for the verification of dose delivery of complex treatments, particularly small fields, compared to treatment planning system calculations. A new radiochromic film, Gafchromic EBT-XD, is available for high-dose treatment verification and we present the first published evaluation of its use. We evaluate the new film for MV photon dosimetry, including calibration curves, performance with single- and triple-channel dosimetry, and comparison to existing EBT3 film. In the verification of a typical 25 Gy stereotactic radiotherapy (SRS) treatment, compared to TPS planned dose distribution, excellent agreement was seen with EBT-XD using triple-channel dosimetry, in isodose overlay, maximum 1.0 mm difference over 200-2400 cGy, and gamma evaluation, mean passing rate 97% at 3% locally-normalised, 1.5 mm criteria. In comparison to EBT3, EBT-XD gave improved evaluation results for the SRS-plan, had improved calibration curve gradients at high doses, and had reduced lateral scanner effect. The dimensions of the two films are identical. The optical density of EBT-XD is lower than EBT3 for the same dose. The effective atomic number for both may be considered water-equivalent in MV radiotherapy. We have validated the use of EBT-XD for high-dose, small-field radiotherapy, for routine QC and a forthcoming multi-centre SRS dosimetry intercomparison.

Evaluation of Gafchromic EBT-XD film, with comparison to EBT3 film, and application in high dose radiotherapy verification

NASA Astrophysics Data System (ADS)

Palmer, Antony L.; Dimitriadis, Alexis; Nisbet, Andrew; Clark, Catharine H.

2015-11-01

There is renewed interest in film dosimetry for the verification of dose delivery of complex treatments, particularly small fields, compared to treatment planning system calculations. A new radiochromic film, Gafchromic EBT-XD, is available for high-dose treatment verification and we present the first published evaluation of its use. We evaluate the new film for MV photon dosimetry, including calibration curves, performance with single- and triple-channel dosimetry, and comparison to existing EBT3 film. In the verification of a typical 25 Gy stereotactic radiotherapy (SRS) treatment, compared to TPS planned dose distribution, excellent agreement was seen with EBT-XD using triple-channel dosimetry, in isodose overlay, maximum 1.0 mm difference over 200-2400 cGy, and gamma evaluation, mean passing rate 97% at 3% locally-normalised, 1.5 mm criteria. In comparison to EBT3, EBT-XD gave improved evaluation results for the SRS-plan, had improved calibration curve gradients at high doses, and had reduced lateral scanner effect. The dimensions of the two films are identical. The optical density of EBT-XD is lower than EBT3 for the same dose. The effective atomic number for both may be considered water-equivalent in MV radiotherapy. We have validated the use of EBT-XD for high-dose, small-field radiotherapy, for routine QC and a forthcoming multi-centre SRS dosimetry intercomparison.

Impact of spot charge inaccuracies in IMPT treatments.

PubMed

Kraan, Aafke C; Depauw, Nicolas; Clasie, Ben; Giunta, Marina; Madden, Tom; Kooy, Hanne M

2017-08-01

Spot charge is one parameter of pencil-beam scanning dose delivery system whose accuracy is typically high but whose required value has not been investigated. In this work we quantify the dose impact of spot charge inaccuracies on the dose distribution in patients. Knowing the effect of charge errors is relevant for conventional proton machines, as well as for new generation proton machines, where ensuring accurate charge may be challenging. Through perturbation of spot charge in treatment plans for seven patients and a phantom, we evaluated the dose impact of absolute (up to 5× 10 6 protons) and relative (up to 30%) charge errors. We investigated the dependence on beam width by studying scenarios with small, medium and large beam sizes. Treatment plan statistics included the Γ passing rate, dose-volume-histograms and dose differences. The allowable absolute charge error for small spot plans was about 2× 10 6 protons. Larger limits would be allowed if larger spots were used. For relative errors, the maximum allowable error size for small, medium and large spots was about 13%, 8% and 6% for small, medium and large spots, respectively. Dose distributions turned out to be surprisingly robust against random spot charge perturbation. Our study suggests that ensuring spot charge errors as small as 1-2% as is commonly aimed at in conventional proton therapy machines, is clinically not strictly needed. © 2017 American Association of Physicists in Medicine.

Benefit of particle therapy in re-irradiation of head and neck patients. Results of a multicentric in silico ROCOCO trial.

PubMed

Eekers, Daniëlle B P; Roelofs, Erik; Jelen, Urszula; Kirk, Maura; Granzier, Marlies; Ammazzalorso, Filippo; Ahn, Peter H; Janssens, Geert O R J; Hoebers, Frank J P; Friedmann, Tobias; Solberg, Timothy; Walsh, Sean; Troost, Esther G C; Kaanders, Johannes H A M; Lambin, Philippe

2016-12-01

In this multicentric in silico trial we compared photon, proton, and carbon-ion radiotherapy plans for re-irradiation of patients with squamous cell carcinoma of the head and neck (HNSCC) regarding dose to tumour and doses to surrounding organs at risk (OARs). Twenty-five HNSCC patients with a second new or recurrent cancer after previous irradiation (70Gy) were included. Intensity-modulated proton therapy (IMPT) and ion therapy (IMIT) re-irradiation plans to a second subsequent dose of 70Gy were compared to photon therapy delivered with volumetric modulated arc therapy (VMAT). When comparing IMIT and IMPT to VMAT, the mean dose to all investigated 22 OARs was significantly reduced for IMIT and to 15 out of 22 OARs (68%) using IMPT. The maximum dose to 2% volume (D 2 ) of the brainstem and spinal cord were significantly reduced using IMPT and IMIT compared to VMAT. The data are available on www.cancerdata.org. In this ROCOCO in silico trial, a reduction in mean dose to OARs was achieved using particle therapy compared to photons in the re-irradiation of HNSCC. There was a dosimetric benefit favouring carbon-ions above proton therapy. These dose reductions may potentially translate into lower severe complication rates related to the re-irradiation. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Study of dosimetric variation due to interfraction organ movement in High Dose Rate Interstital (MUPIT) brachytherapy for gynecologic malignancies

NASA Astrophysics Data System (ADS)

Velmurugan, Thanigaimalai; Sukumar, Prabakar; Krishnappan, Chokkalingam; Boopathy, Raghavendiran

2010-01-01

Ten patients with cancer of uterine cervix who underwent interstitial brachytherapy using MUPIT templates were CT scanned (CT1) using which bladder, rectum and CTV were delineated. The treatment plan PCT1 was generated and optimized geometrically on the volume. CT scan (CT2) was repeated before the second fraction of the treatment CTV and critical organs were delineated. The plan (PCT2) was created by reproducing the Plan PCT1 in the CT2 images and compared with PCT1. Bladder, Rectum and CTV percentage volume variation ranges from +28.6% to -34.3%, 38.4% to -14.9% and 8.5% to -15.2% respectively. Maximum dose variation in bladder was +17.1%, in rectum was up to +410% and in CTV was -13.0%. The dose to these structures varies independently with no strong correlation with the volume variation. Hence it is suggested that repeat CT and re-planning is mandatory before second fraction execution.

Dosimetry of Strontium eye applicator: Comparison of Monte Carlo calculations and radiochromic film measurements

NASA Astrophysics Data System (ADS)

Laoues, M.; Khelifi, R.; Moussa, A. S.

2015-01-01

Strontium-90 eye applicators are a beta-ray emitter with a relatively high-energy (maximum energy about 2.28 MeV and average energy about 0.9 MeV). These applicators come in different shapes and dimensions; they are used for the treatment of eye diseases. Whenever, radiation is used in treatment, dosimetry is essential. However, knowledge of the exact dose distribution is a critical decision-making to the outcome of the treatment. The main aim of our study is to simulate the dosimetry of the SIA.20 eye applicator with Monte Carlo GATE 6.1 platform and to compare the calculated results with those measured with EBT2 films. This means that GATE and EBT2 were used to quantify the surface and depths dose- rate, the relative dose profile and the dosimetric parameters in according to international recommendations. Calculated and measured results are in good agreement and they are consistent with the ICRU and NCS recommendations.

SU-G-BRC-16: Theory and Clinical Implications of the Constant Dosimetric Leaf Gap (DLG) Approximation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumaraswamy, L; Xu, Z; Podgorsak, M

Purpose: Commercial dose calculation algorithms incorporate a single DLG value for a given beam energy that is applied across an entire treatment field. However, the physical processes associated with beam generation and dose delivery suggest that the DLG is not constant. The aim of this study is to evaluate the variation of DLG among all leaf pairs, to quantify how this variation impacts delivered dose, and to establish a novel method to correct dose distributions calculated using the approximation of constant DLG. Methods: A 2D diode array was used to measure the DLG for all 60 leaf pairs at severalmore » points along each leaf pair travel direction. This approach was validated by comparison to DLG values measured at select points using a 0.6 cc ion chamber with the standard formalism. In-house software was developed to enable incorporation of position dependent DLG values into dose distribution optimization and calculation. The accuracy of beam delivery of both the corrected and uncorrected treatment plans was studied through gamma pass rate evaluation. A comparison of DVH statistics in corrected and uncorrected treatment plans was made. Results: The outer 20 MLC leaf pairs (1.0 cm width) have DLG values that are 0.32 mm (mean) to 0.65 mm (maximum) lower than the central leaf-pair. VMAT plans using a large number of 1 cm wide leaves were more accurately delivered (gamma pass rate increased by 5%) and dose coverage was higher (D100 increased by 3%) when the 2D DLG was modeled. Conclusion: Using a constant DLG value for a given beam energy will result in dose optimization, dose calculation and treatment delivery inaccuracies that become significant for treatment plans with high modulation complexity scores delivered with 1 cm wide leaves.« less

Pediatric 131I-MIBG Therapy for Neuroblastoma: Whole-Body 131I-MIBG Clearance, Radiation Doses to Patients, Family Caregivers, Medical Staff, and Radiation Safety Measures.

PubMed

Willegaignon, José; Crema, Karin Paola; Oliveira, Nathaliê Canhameiro; Pelissoni, Rogério Alexandre; Coura-Filho, George Barberio; Sapienza, Marcelo Tatit; Buchpiguel, Carlos Alberto

2018-06-19

I-metaiodobenzylguanidine (I-MIBG) has been used in the diagnosis and therapy of neuroblastoma in adult and pediatric patients for many years. In this study, we evaluated whole-body I-MIBG clearance and radiation doses received by patients, family caregivers, and medical staff to establish appropriate radiation safety measures to be used in therapy applications. Research was focused on 23 children and adolescents with metastatic neuroblastoma, with ages ranging from 1.8 to 13 years, being treated with I-MIBG. Based on measured external dose rates from patients, dosimetric data to patients, family members, and others were calculated. The mean ± SD I-MIBG activity administered was 8.55 ± 1.69 GBq. Percent whole-body retention rates of I-MIBG at 24, 48, and 72 hours after administration were 48% ± 7%, 23% ± 7%, and 12% ± 6%, with a whole-body I-MIBG effective half-life of 23 ± 5 hours for all patients. The mean doses for patients were 0.234 ± 0.096 mGy·MBq to red-marrow and 0.251 ± 0.101 mGy·MBq to whole body. The maximum potential radiation doses transmitted by patients to others at 1.0 m was estimated to be 11.9 ± 3.4 mSv, with 97% of this dose occurring over 120 hours after therapy administration. Measured mean dose received by the 22 family caregivers was 1.88 ± 1.85 mSv, and that received by the 19 pediatric physicians was 43 ± 51 μSv. In this study, we evaluated the whole-body clearance of I-MIBG in 23 pediatric patients, and the radiation doses received by family caregivers and medical staff during these therapy procedures, thus facilitating the establishment of radiation safety measures to be applied in pediatric therapy.

A phase I-II study of paclitaxel, ifosfamide, and vinorelbine with filgrastim (rhG-CSF) support in advanced non-small-cell lung cancer.

PubMed

Masters, G A; Mauer, A M; Hoffman, P C; Wyka, D; Samuels, B L; Krauss, S A; Watson, S; Golomb, H; Vokes, E E

1998-06-01

We designed a phase I-II trial of three active agents, paclitaxel, ifosfamide, and vinorelbine, in advanced non-small-cell lung cancer (NSCLC) to: 1) define the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of paclitaxel with filgrastim (G-CSF) support; and 2) determine the overall response rate and median survival of patients treated on this regimen. We treated cohorts of patients with stage IIIB or IV NSCLC with ifosfamide 1.2-1.6 g/m2/day x 3 and vinorelbine 20-25 mg/m2/day x 3 and escalating doses of paclitaxel at 100-175 mg/m2 on day 2 with G-CSF support on a 21-day cycle. One prior experimental single-agent chemotherapy regimen was allowed. Fifty-six patients, were enrolled on this trial: 27 on the phase I portion of the study and an additional 29 at the recommended phase II dose (RPTD). Thirteen patients had received prior chemotherapy. Paclitaxel doses of 175 mg/m2 and 150 mg/m2 produced dose-limiting myelosuppression, and the RPTD was determined to be paclitaxel 135 mg/m2 with ifosfamide 1.2 g/m2/day on days 1-3 and vinorelbine 20 mg/m2/ day on days 1-3 with G-CSF support. The overall response rate was 18%, with a median survival of 6.1 months. Six of 35 patients (17%) treated at the RPTD achieved a partial response to therapy. Grade IV neutropenia was observed in 19 of 35 patients at this dose, with eight patients suffering febrile neutropenia. This non-cisplatin-containing three-drug regimen has substantial toxicity and low activity in advanced NSCLC, and does not seem to improve on prior regimens. It is unclear whether the lack of efficacy relates to an antagonistic reaction between the specific drugs, administration schedule, or to subtherapeutic doses of the individual agents.

SU-F-BRE-07: Experimental Validation of a Lung SBRT Technique Using a Novel, True Volumetric Plenoptic-Plastic-Scintillator Detector

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goulet, M; Rilling, M; Gingras, L

2014-06-15

Purpose: Lung SBRT is being used by an increasing number of clinics, including our center which recently treated its first patient. In order to validate this technique, the 3D dose distribution of the SBRT plan was measured using a previously developed 3D detector based on plenoptic camera and plastic scintillator technology. The excellent agreement between the detector measurement and the expected dose from the treatment planning system Pinnacle{sup 3} shows great promise and amply justify the development of the technique. Methods: The SBRT treatment comprised 8 non-coplanar 6MV photon fields with a mean field size of 12 cm{sup 2} atmore » isocentre and a total prescription dose of 12Gy per fraction for a total of 48Gy. The 3D detector was composed of a 10×10×10 cm{sup 2} EJ-260 water-equivalent plastic scintillator embedded inside a truncated cylindrical acrylic phantom of 10cm radius. The scintillation light was recorded using a static R5 light-field camera and the 3D dose was reconstructed at a 2mm resolution in all 3 dimensions using an iterative backprojection algorithm. Results: The whole 3D dose distribution was recorded at a rate of one acquisition per second. The mean absolute dose difference between the detector and Pinnacle{sup 3} was 1.3% over the region with more than 10% of the maximum dose. 3D gamma tests performed over the same region yield passing rates of 98.8% and 96.6% with criteria of 3%/1mm and 2%/1mm, respectively. Conclusion: Experimental results showed that our beam modeling and treatment planning system calculation was adequate for the safe administration of small field/high dose techniques such as SBRT. Moreover, because of the real-time capability of the detector, further validation of small field rotational, dynamic or gated technique can be monitored or verified by this system.« less

Labetalol compared with propranolol in the treatment of black hypertensive patients.

PubMed

Saunders, E; Curry, C; Hinds, J; Kong, B W; Medakovic, M; Poland, M; Roper, K

1987-09-01

A double-blind parallel group study was conducted to examine the effects of oral labetalol, in doses from 100 to 800 mg BID, and propranolol, 40 to 320 mg, in patients with mild to moderate hypertension. The doses of labetalol (n = 74) and propranolol (n = 79) were titrated weekly to achieve a sitting diastolic blood pressure (DBP) of less than 90 mmHg or at least a 10-mmHg decrease from placebo baseline on two consecutive visits. A 2-month fixed-dose maintenance phase followed in which a diuretic could be added if the sitting DBP was greater than or equal to 100 mmHg on maximum doses of either drug. BP and heart rate were measured 8-12 hours after a dose in the sitting and standing positions. Labetalol was significantly more effective at the end of monotherapy than propranolol was in lowering both the sitting (p less than .05) and standing (p less than .04) DBP. The reduction in the systolic, although more pronounced for those on labetalol, was not significantly different; 53% of patients had a "good" response to labetalol compared with 30% of the propranolol group. Propranolol significantly (p less than 0.01) lowered heart rate compared with labetalol. Nine patients in the labetalol group and 10 in the propranolol group required a diuretic. The decrease in BP after the addition of a diuretic was comparable. Changes in plasma lipids were not significant, but HDL increased 9% with labetalol and decreased 2% with propranolol. Triglycerides increased 25% with labetalol and 31% with propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Volumetric-modulated arc therapy (VMAT) for whole brain radiotherapy: not only for hippocampal sparing, but also for reduction of dose to organs at risk.

PubMed

Sood, Sumit; Pokhrel, Damodar; McClinton, Christopher; Lominska, Christopher; Badkul, Rajeev; Jiang, Hongyu; Wang, Fen

2017-01-01

A prospective clinical trial, Radiation Therapy Oncology Group (RTOG) 0933, has demonstrated that whole brain radiotherapy (WBRT) using conformal radiation delivery technique with hippocampal avoidance is associated with less memory complications. Further sparing of other organs at risk (OARs) including the scalp, ear canals, cochleae, and parotid glands could be associated with reductions in additional toxicities for patients treated with WBRT. We investigated the feasibility of WBRT using volumetric-modulated arc therapy (VMAT) to spare the hippocampi and the aforementioned OARs. Ten patients previously treated with nonconformal WBRT (NC-WBRT) using opposed lateral beams were retrospectively re-planned using VMAT with hippocampal sparing according to the RTOG 0933 protocol. The OARs (scalp, auditory canals, cochleae, and parotid glands) were considered as dose-constrained structures. VMAT plans were generated for a prescription dose of 30 Gy in 10 fractions. Comparison of the dosimetric parameters achieved by VMAT and NC-WBRT plans was performed using paired t-tests using upper bound p-value of < 0.001. Average beam on time and monitor units (MUs) delivered to the patients on VMAT were compared with those obtained with NC-WBRT. All VMAT plans met RTOG 0933 dosimetric criteria including the dose to hippocampi of 100% of the volume (D 100% ) of 8.4 ± 0.3 Gy and maximum dose of 15.6 ± 0.4 Gy, respectively. A statistically significant dose reduction (p < 0.001) to all OARs was achieved. The mean and maximum scalp doses were reduced by an average of 9 Gy (32%) and 2 Gy (6%), respectively. The mean and maximum doses to the auditory canals were reduced from 29.5 ± 0.5 Gy and 31.0 ± 0.4 Gy with NC-WBRT, to 21.8 ± 1.6 Gy (26%) and 27.4 ± 1.4 Gy (12%) with VMAT. VMAT also reduced mean and maximum doses to the cochlea by an average of 4 Gy (13%) and 2 Gy (6%), respectively. The parotid glands mean and maximum doses with VMAT were 4.4 ± 1.9 Gy and 15.7 ± 5.0 Gy, compared to 12.8 ± 4.9 Gy and 30.6 ± 0.5 Gy with NC-WBRT, respectively. The average dose reduction of mean and maximum of parotid glands from VMAT were 65% and 50%, respectively. The average beam on time and MUs were 2.3minutes and 719 on VMAT, and 0.7 minutes and 350 on NC-WBRT. This study demonstrated the feasibility of WBRT using VMAT to not only spare the hippocampi, but also significantly reduce dose to OARs. These advantages of VMAT could potentially decrease the toxicities associated with NC-WBRT and improve patients' quality of life, especially for patients with favorable prognosis receiving WBRT or patients receiving prophylactic cranial irradiation (PCI). Published by Elsevier Inc.

A phase I study with neratinib (HKI-272), an irreversible pan ErbB receptor tyrosine kinase inhibitor, in patients with solid tumors.

PubMed

Wong, Kwok-K; Fracasso, Paula M; Bukowski, Ronald M; Lynch, Thomas J; Munster, Pamela N; Shapiro, Geoffrey I; Jänne, Pasi A; Eder, Joseph P; Naughton, Michael J; Ellis, Matthew J; Jones, Suzanne F; Mekhail, Tarek; Zacharchuk, Charles; Vermette, Jennifer; Abbas, Richat; Quinn, Susan; Powell, Christine; Burris, Howard A

2009-04-01

The dose-limiting toxicities, maximum tolerated dose, pharmacokinetic profile, and preliminary antitumor activity of neratinib (HKI-272), an irreversible pan ErbB inhibitor, were determined in patients with advanced solid tumors. Neratinib was administered orally as a single dose, followed by a 1-week observation period, and then once daily continuously. Planned dose escalation was 40, 80, 120, 180, 240, 320, 400, and 500 mg. For pharmacokinetic analysis, timed blood samples were collected after administration of the single dose and after the first 14 days of continuous daily administration. Dose-limiting toxicity was grade 3 diarrhea, which occurred in one patient treated with 180 mg and in four patients treated with 400 mg neratinib; hence, the maximum tolerated dose was determined to be 320 mg. Other common neratinib-related toxicities included nausea, vomiting, fatigue, and anorexia. Exposure to neratinib was dose dependent, and the pharmacokinetic profile of neratinib supports a once-a-day dosing regimen. Partial response was observed for 8 (32%) of the 25 evaluable patients with breast cancer. Stable disease >or=24 weeks was observed in one evaluable breast cancer patient and 6 (43%) of the 14 evaluable non-small cell lung cancer patients. The maximum tolerated dose of once-daily oral neratinib is 320 mg. The most common neratinib-related toxicity was diarrhea. Antitumor activity was observed in patients with breast cancer who had previous treatment with trastuzumab, anthracyclines, and taxanes, and tumors with a baseline ErbB-2 immunohistochemical staining intensity of 2+ or 3+. The antitumor activity, tolerable toxicity profile, and pharmacokinetic properties of neratinib warrant its further evaluation.

Implementation of a dose gradient method into optimization of dose distribution in prostate cancer 3D-CRT plans

PubMed Central

Giżyńska, Marta K.; Kukołowicz, Paweł F.; Kordowski, Paweł

2014-01-01

Aim The aim of this work is to present a method of beam weight and wedge angle optimization for patients with prostate cancer. Background 3D-CRT is usually realized with forward planning based on a trial and error method. Several authors have published a few methods of beam weight optimization applicable to the 3D-CRT. Still, none on these methods is in common use. Materials and methods Optimization is based on the assumption that the best plan is achieved if dose gradient at ICRU point is equal to zero. Our optimization algorithm requires beam quality index, depth of maximum dose, profiles of wedged fields and maximum dose to femoral heads. The method was tested for 10 patients with prostate cancer, treated with the 3-field technique. Optimized plans were compared with plans prepared by 12 experienced planners. Dose standard deviation in target volume, and minimum and maximum doses were analyzed. Results The quality of plans obtained with the proposed optimization algorithms was comparable to that prepared by experienced planners. Mean difference in target dose standard deviation was 0.1% in favor of the plans prepared by planners for optimization of beam weights and wedge angles. Introducing a correction factor for patient body outline for dose gradient at ICRU point improved dose distribution homogeneity. On average, a 0.1% lower standard deviation was achieved with the optimization algorithm. No significant difference in mean dose–volume histogram for the rectum was observed. Conclusions Optimization shortens very much time planning. The average planning time was 5 min and less than a minute for forward and computer optimization, respectively. PMID:25337411

Comparison of TID Effects in Space-Like Variable Dose Rates and Constant Dose Rates

NASA Technical Reports Server (NTRS)

Harris, Richard D.; McClure, Steven S.; Rax, Bernard G.; Evans, Robin W.; Jun, Insoo

2008-01-01

The degradation of the LM193 dual voltage comparator has been studied at different TID dose rate profiles, including several different constant dose rates and a variable dose rate that simulates the behavior of a solar flare. A comparison of results following constant dose rate vs. variable dose rates is made to explore how well the constant dose rates used for typical part testing predict the performance during a simulated space-like mission. Testing at a constant dose rate equal to the lowest dose rate seen during the simulated flare provides an extremely conservative estimate of the overall amount of degradation. A constant dose rate equal to the average dose rate is also more conservative than the variable rate. It appears that, for this part, weighting the dose rates by the amount of total dose received at each rate (rather than the amount of time at each dose rate) results in an average rate that produces an amount of degradation that is a reasonable approximation to that received by the variable rate.

Dependence of normal brain integral dose and normal tissue complication probability on the prescription isodose values for γ-knife radiosurgery

NASA Astrophysics Data System (ADS)

Ma, Lijun

2001-11-01

A recent multi-institutional clinical study suggested possible benefits of lowering the prescription isodose lines for stereotactic radiosurgery procedures. In this study, we investigate the dependence of the normal brain integral dose and the normal tissue complication probability (NTCP) on the prescription isodose values for γ-knife radiosurgery. An analytical dose model was developed for γ-knife treatment planning. The dose model was commissioned by fitting the measured dose profiles for each helmet size. The dose model was validated by comparing its results with the Leksell gamma plan (LGP, version 5.30) calculations. The normal brain integral dose and the NTCP were computed and analysed for an ensemble of treatment cases. The functional dependence of the normal brain integral dose and the NCTP versus the prescribing isodose values was studied for these cases. We found that the normal brain integral dose and the NTCP increase significantly when lowering the prescription isodose lines from 50% to 35% of the maximum tumour dose. Alternatively, the normal brain integral dose and the NTCP decrease significantly when raising the prescribing isodose lines from 50% to 65% of the maximum tumour dose. The results may be used as a guideline for designing future dose escalation studies for γ-knife applications.

Radiation effects program

NASA Astrophysics Data System (ADS)

1985-09-01

No existing LINAC Based Beam Heating facility comes within a factor of ten of the needs of a high heating rate thermodynamic properties research facility. The facility could be built at the Naval Research Lab. for a cost in the neighborhood of 2 million dollars. The 10 MeV electron beam would not produce any serious radioactivity but would provide unprecedented beam power for such other applications as food processing, sewer treatment, materials curing, radiation hardness assurance, etc. One can always achieve lower current densities by scattering the beam and moving the device under test further away from the scatterer. In this case one must rely on the TLD readings to indicate the dose rate at the point of interest. For general utility with the beam covering about four TLD's fairly evenly one can claim that the NRL LINAC can produce a maximum dose rate of about 6 x 10 to the 10th power rads (Si) per second for a pulse length of 1.5 microseconds, and about 1.4 x 10 to the 11th power rads (Si) per second in a 50 nanosecond pulse. In both cases the beam area is about 0.4 square centimeters.

Sensory irritation and incapacitation evoked by thermal decomposition products of polymers and comparisons with known sensory irritants.

PubMed

Barrow, C S; Alarie, Y; Stock, M F

1978-01-01

A decrease in respiratory rate in mice during exposure to irritating airborne chemicals has been utilized as a response parameter to characterize the degree of upper respiratory tract irritation (sensory irritation) to the thermal decomposition products of various polymers. These included polystyrene, polyvinyl chloride, flexible polyurethane foam, polytetrafluorethylene, a fiber glass reinforced polyester resin, and Douglas Fir. Each of the materials was thermally decomposed in a low-mass vertical furnace in an air atmosphere at a programmed heating rate of 20 degrees C/min. Mice, in groups of four, were exposed to graded concentrations of the thermal decomposition products of each of the above materials. Dose-response curves were obtained by utilizing the maximum percent decrease in respiratory rate as the response parameter during each exposure. Comparison of these dose-response curves with other sensory irritants such as chlorine, ammonia, hydrogen chloride, sulfur dioxide, and toluene diisocyanate gave an indication of the sensory irrtation potential of the thermal decomposition products of these various polymers versus that of well-known single airborne chemical irritants. Total stress and incapacitation of the organism during exposure to sensory irritants such as from the thermal decomposition products of synthetic polymers is discussed.

Consequences of the river valley bottom transformation after extreme flood (on the example of the Niida River, Japan)

NASA Astrophysics Data System (ADS)

Botavin, D.; Golosov, V.; Konoplev, A.; Wakiyama, Y.

2018-01-01

Detailed study of different sections of floodplain was undertaken in the Niida River basin (Fukushima Prefecture) after an extreme flood event which occurred in the middle of September 2015. The upstream part of the basin is located in the area with very high level of radionuclide contamination after the accident at Fukushima Dai-ichi NPP. Field and GIS methods were used, including direct measurement of the depth of fresh sediment and its area, with soil descriptions for the typical floodplain sections, measurement of dose rates, interpretation of space images for a few time intervals (before and after flood event) with the following evaluation of spatial changes in deposition for different floodplain sections. In addition, results of quantitative assessment of sedimentation rates and soil radionuclide contamination were applied for understanding the effect of extreme flood on alluvial soils of the different sections. It was established that the maximum sedimentation rates (20-50 cm/event) occurred in the middle part of the lower reach of the Niida River and in some locations of the upper reaches. Dose rates had reduced considerably for all the areas with high sedimentation because the top soil layers with high radionuclide contamination were buried under fresh sediments produced mostly due to bank erosion and mass movements.

Feasibility of Administering High-Dose 131I-MIBG Therapy to Children with High-Risk Neuroblastoma without Lead-Lined Rooms

PubMed Central

Chu, Bae P.; Horan, Christopher; Basu, Ellen; Dauer, Lawrence; Williamson, Matthew; Carrasquillo, Jorge A.; Pandit-Taskar, Neeta; Modak, Shakeel

2015-01-01

Background Although 131I-metaiodobenzylguanidine therapy (131I-MIBG) is increasingly used for children with high-risk neuroblastoma, a paucity of lead-lined rooms limits its wider use. We implemented radiation safety procedures to comply with New York City Department of Health and Mental Hygiene regulations for therapeutic radioisotopes and administered 131I-MIBG using rolling lead shields. Procedure Patients received 0.67GBq (18mCi)/kg/dose 131I-MIBG on an IRB-approved protocol (NCT00107289). Radiation safety procedures included private room with installation of rolling lead shields to maintain area dose rates ≤0.02mSv/h outside the room, patient isolation until dose rate <0.07mSv/h at 1m and retention of a urinary catheter with collection of urine in lead boxes. Parents were permitted in the patient’s room behind lead shields, trained in radiation safety principles and given real-time radiation monitors. Results Records on 16 131I-MIBG infusions among 10 patients (age 2–11 years) were reviewed. Mean ± standard deviation 131I-MIBG administered was 17.67±11.14 (range: 6.11–40.59) GBq. Mean maximum dose rates outside treatment rooms were 0.013±0.008 mSv/hr. Median time-to-discharge was 3 days post-131I-MIBG. Exposure of medical staff and parents was below regulatory limits. Cumulative whole-body dose received by the physician, nurse and radiation safety officer during treatment was 0.098±0.058, 0.056±0.045, 0.055±0.050 mSv respectively. Cumulative exposure to parents was 0.978±0.579mSv. Estimated annual radiation exposure for inpatient nurses was 0.096±0.034mSv/nurse. Thyroid bioassay scans on all medical personnel were

SU-F-T-117: A Pilot Study of Organ Dose Reconstruction for Wilms Tumor Patients Treated with Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Makkia, R; Pelletier, C; Jung, J

Purpose: To reconstruct major organ doses for the Wilms tumor pediatric patients treated with radiation therapy using pediatric computational phantoms, treatment planning system (TPS), and Monte Carlo (MC) dose calculation methods. Methods: A total of ten female and male pediatric patients (15–88 months old) were selected from the National Wilms Tumor Study cohort and ten pediatric computational phantoms corresponding to the patient’s height and weight were selected for the organ dose reconstruction. Treatment plans were reconstructed on the computational phantoms in a Pinnacle TPS (v9.10) referring to treatment records and exported into DICOM-RT files, which were then used to generatemore » the input files for XVMC MC code. The mean doses to major organs and the dose received by 50% of the heart were calculated and compared between TPS and MC calculations. The same calculations were conducted by replacing the computational human phantoms with a series of diagnostic patient CT images selected by matching the height and weight of the patients to validate the anatomical accuracy of the computational phantoms. Results: Dose to organs located within the treatment fields from the computational phantoms and the diagnostic patient CT images agreed within 2% for all cases for both TPS and MC calculations. The maximum difference of organ doses was 55.9 % (thyroid), but the absolute dose difference in this case was 0.33 Gy which was 0.96% of the prescription dose. The doses to ovaries and testes from MC in out-of-field provided more discrepancy (the maximum difference of 13.2% and 50.8%, respectively). The maximum difference of the 50% heart volume dose between the phantoms and the patient CT images was 40.0%. Conclusion: This study showed the pediatric computational phantoms are applicable to organ doses reconstruction for the radiotherapy patients whose three-dimensional radiological images are not available.« less

Direct plan comparison of RapidArc and CyberKnife for spine stereotactic body radiation therapy

NASA Astrophysics Data System (ADS)

Choi, Young Eun; Kwak, Jungwon; Song, Si Yeol; Choi, Eun Kyung; Ahn, Seung Do; Cho, Byungchul

2015-07-01

We compared the treatment planning performance of RapidArc (RA) vs. CyberKnife (CK) for spinal stereotactic body radiation therapy (SBRT). Ten patients with spinal lesions who had been treated with CK were re-planned with RA, which consisted of two complete arcs. Computed tomography (CT) and volumetric dose data of CK, generated using the Multiplan (Accuray) treatment planning system (TPS) and the Ray-trace algorithm, were imported to Varian Eclipse TPS in Dicom format, and the data were compared with the RA plan by using an analytical anisotropic algorithm (AAA) dose calculation. The optimized dose priorities for both the CK and the RA plans were similar for all patients. The highest priority was to provide enough dose coverage to the planned target volume (PTV) while limiting the maximum dose to the spinal cord. Plan quality was evaluated with respect to PTV coverage, conformity index (CI), high-dose spillage, intermediate-dose spillage (R50% and D2cm), and maximum dose to the spinal cord, which are criteria recommended by the RTOG 0631 spine and 0915 lung SBRT protocols. The mean CI' SD values of the PTV were 1.11' 0.03 and 1.17' 0.10 for RA and CK ( p = 0.02), respectively. On average, the maximum dose delivered to the spinal cord in CK plans was approximately 11.6% higher than that in RA plans, and this difference was statistically significant ( p < 0.001). High-dose spillages were 0.86% and 2.26% for RA and CK ( p = 0.203), respectively. Intermediate-dose spillage characterized by D2cm was lower for RA than for CK; however, R50% was not statistically different. Even though both systems can create highly conformal volumetric dose distributions, the current study shows that RA demonstrates lower high- and intermediate-dose spillages than CK. Therefore, RA plans for spinal SBRT may be superior to CK plans.

Maximum likelihood analysis of bioassay data from long-term follow-up of two refractory PuO2 inhalation cases.

PubMed

Avtandilashvili, Maia; Brey, Richard; James, Anthony C

2012-07-01

The U.S. Transuranium and Uranium Registries' tissue donors 0202 and 0407 are the two most highly exposed of the 18 registrants who were involved in the 1965 plutonium fire accident at a defense nuclear facility. Material released during the fire was well characterized as "high fired" refractory plutonium dioxide with 0.32-μm mass median diameter. The extensive bioassay data from long-term follow-up of these two cases were used to evaluate the applicability of the Human Respiratory Tract Model presented by International Commission on Radiological Protection in Publication 66 and its revision proposed by Gregoratto et al. in order to account for the observed long-term retention of insoluble material in the lungs. The maximum likelihood method was used to calculate the point estimates of intake and tissue doses and to examine the effect of different lung clearance, blood absorption, and systemic models on the goodness-of-fit and estimated dose values. With appropriate adjustments, Gregoratto et al. particle transport model coupled with the customized blood absorption parameters yielded a credible fit to the bioassay data for both cases and predicted the Case 0202 liver and skeletal activities measured postmortem. PuO2 particles produced by the plutonium fire are extremely insoluble. About 1% of this material is absorbed from the respiratory tract relatively rapidly, at a rate of about 1 to 2 d (half-time about 8 to 16 h). The remainder (99%) is absorbed extremely slowly, at a rate of about 5 × 10(-6) d (half-time about 400 y). When considering this situation, it appears that doses to other body organs are negligible in comparison to those to tissues of the respiratory tract. About 96% of the total committed weighted dose equivalent is contributed by the lungs. Doses absorbed by these workers' lungs were high: 3.2 Gy to AI and 6.5 Gy to LNTH for Case 0202 (18 y post-intake) and 3.2 Gy to AI and 55.5 Gy to LNTH for Case 0407 (43 y post-intake). This evaluation supports the Gregoratto et al. proposed revision to the ICRP 66 model when considering situations of extremely insoluble particles.

Sensitivity of 3D Dose Verification to Multileaf Collimator Misalignments in Stereotactic Body Radiation Therapy of Spinal Tumor.

PubMed

Xin-Ye, Ni; Ren, Lei; Yan, Hui; Yin, Fang-Fang

2016-12-01

This study aimed to detect the sensitivity of Delt 4 on ordinary field multileaf collimator misalignments, system misalignments, random misalignments, and misalignments caused by gravity of the multileaf collimator in stereotactic body radiation therapy. (1) Two field sizes, including 2.00 cm (X) × 6.00 cm (Y) and 7.00 cm (X) × 6.00 cm (Y), were set. The leaves of X1 and X2 in the multileaf collimator were simultaneously opened. (2) Three cases of stereotactic body radiation therapy of spinal tumor were used. The dose of the planning target volume was 1800 cGy with 3 fractions. The 4 types to be simulated included (1) the leaves of X1 and X2 in the multileaf collimator were simultaneously opened, (2) only X1 of the multileaf collimator and the unilateral leaf were opened, (3) the leaves of X1 and X2 in the multileaf collimator were randomly opened, and (4) gravity effect was simulated. The leaves of X1 and X2 in the multileaf collimator shifted to the same direction. The difference between the corresponding 3-dimensional dose distribution measured by Delt 4 and the dose distribution in the original plan made in the treatment planning system was analyzed with γ index criteria of 3.0 mm/3.0%, 2.5 mm/2.5%, 2.0 mm/2.0%, 2.5 mm/1.5%, and 1.0 mm/1.0%. (1) In the field size of 2.00 cm (X) × 6.00 cm (Y), the γ pass rate of the original was 100% with 2.5 mm/2.5% as the statistical standard. The pass rate decreased to 95.9% and 89.4% when the X1 and X2 directions of the multileaf collimator were opened within 0.3 and 0.5 mm, respectively. In the field size of 7.00 (X) cm × 6.00 (Y) cm with 1.5 mm/1.5% as the statistical standard, the pass rate of the original was 96.5%. After X1 and X2 of the multileaf collimator were opened within 0.3 mm, the pass rate decreased to lower than 95%. The pass rate was higher than 90% within the 3 mm opening. (2) For spinal tumor, the change in the planning target volume V 18 under various modes calculated using treatment planning system was within 1%. However, the maximum dose deviation of the spinal cord was high. In the spinal cord with a gravity of -0.25 mm, the maximum dose deviation minimally changed and increased by 6.8% than that of the original. In the largest opening of 1.00 mm, the deviation increased by 47.7% than that of the original. Moreover, the pass rate of the original determined through Delt 4 was 100% with 3 mm/3% as the statistical standard. The pass rate was 97.5% in the 0.25 mm opening and higher than 95% in the 0.5 mm opening A, 0.25 mm opening A, whole gravity series, and 0.20 mm random opening. Moreover, the pass rate was higher than 90% with 2.0 mm/2.0% as the statistical standard in the original and in the 0.25 mm gravity. The difference in the pass rates was not statistically significant among the -0.25 mm gravity, 0.25 mm opening A, 0.20 mm random opening, and original as calculated using SPSS 11.0 software with P > .05. Different analysis standards of Delt 4 were analyzed in different field sizes to improve the detection sensitivity of the multileaf collimator position on the basis of 90% throughout rate. In stereotactic body radiation therapy of spinal tumor, the 2.0 mm/2.0% standard can reveal the dosimetric differences caused by the minor multileaf collimator position compared with the 3.0 mm/3.0% statistical standard. However, some position derivations of the misalignments that caused high dose amount to the spinal cord cannot be detected. However, some misalignments were not detected when a large number of multileaf collimator were administered into the spinal cord. © The Author(s) 2015.

Fate and effects of nitrogen and phosphorus in shallow vegetated aquatic ecosystems

USGS Publications Warehouse

Fairchild, James F.; Vradenburg, Leigh Ann

2006-01-01

Nitrate concentrations have greatly increased in streams and rivers draining agricultural regions of the Midwestern United States, increasing nitrate transport to the Gulf of Mexico has been implicated in the hypoxic conditions that threaten the productivity of marine fisheries. Increases in nitrate concentrations have been attributed to a combination of factors including agricultural expansion, increased nitrogen application rates, increased tile drainage, and loss of riparian Wetlands, These landscape-level changes have resulted in a decreased natural capacity for nitrogen uptake, removal, and cycling back to the atmosphere. Land managers are increasingly interested in using wetland construction and rehabilitation as a management practice to reduce loss of nitrate from the terrestrial systems. Yet, relatively little is known about the limnological factors involved in nitrate removal by Wetland systems.We conducted a series of studies from 1999-2000 to investigate the functional capacity of shallow, macrophyte-dominated pond wetland systems for uptake, assimilation, and retention of nitrogen (N) and phosphorus (P). We evaluated four factors that were hypothesized to influence nutrient uptake and assimilation: 1) nitrate loading rates; 2) nitrogen to phosphorus (N.P) ratios; 3) frequency of dosing/application; and 4) timing of dose initiation.Nutrient assimilation was rapid; store than 90% of added nutrients were removed from the water column in all treatments. Neither variation in N:P ratios (evaluated range, <13:1 to -114.1), frequency of application (weekly or bi-weekly), nor liming of dose initiation relative to macrophyte development (0%, 15-25%, or 75-90% maximum biomass) had significant effects on nutrient assimilation of wetland community dynamics. Maximum loading of nitrate (60 g N/m2 2.4 g P/m2) applied as six weekly doses stimulated algal communities, but inhibited macrophyte communities.Predicted shifts from a stable state of macrophyte- to phytoplankton-dominance did not occur due to nutrient additions. Macrophytes, phytoplankton, and the sediment surface were all significant factors in the removal of nitrate from the Water column. Overall, these shallow macrophyte-dominated systems provided an efficient means of removing nutrients from the water column. Construction or rehabilitation of shallow, vegetated wetlands may offer promise as land management practices for nutrient removal in agricultural watersheds.

Comparison of Monte Carlo and analytical dose computations for intensity modulated proton therapy

NASA Astrophysics Data System (ADS)

Yepes, Pablo; Adair, Antony; Grosshans, David; Mirkovic, Dragan; Poenisch, Falk; Titt, Uwe; Wang, Qianxia; Mohan, Radhe

2018-02-01

To evaluate the effect of approximations in clinical analytical calculations performed by a treatment planning system (TPS) on dosimetric indices in intensity modulated proton therapy. TPS calculated dose distributions were compared with dose distributions as estimated by Monte Carlo (MC) simulations, calculated with the fast dose calculator (FDC) a system previously benchmarked to full MC. This study analyzed a total of 525 patients for four treatment sites (brain, head-and-neck, thorax and prostate). Dosimetric indices (D02, D05, D20, D50, D95, D98, EUD and Mean Dose) and a gamma-index analysis were utilized to evaluate the differences. The gamma-index passing rates for a 3%/3 mm criterion for voxels with a dose larger than 10% of the maximum dose had a median larger than 98% for all sites. The median difference for all dosimetric indices for target volumes was less than 2% for all cases. However, differences for target volumes as large as 10% were found for 2% of the thoracic patients. For organs at risk (OARs), the median absolute dose difference was smaller than 2 Gy for all indices and cohorts. However, absolute dose differences as large as 10 Gy were found for some small volume organs in brain and head-and-neck patients. This analysis concludes that for a fraction of the patients studied, TPS may overestimate the dose in the target by as much as 10%, while for some OARs the dose could be underestimated by as much as 10 Gy. Monte Carlo dose calculations may be needed to ensure more accurate dose computations to improve target coverage and sparing of OARs in proton therapy.